Human Antigen Binding Proteins That Bind To a Complex Comprising beta-Klotho and an FGF Receptor

ABSTRACT

The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing B-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

This application is a division of U.S. application Ser. No. 13/487,061(filed Jun. 1, 2012), which claims the benefit of U.S. ProvisionalApplication Nos. 61/493,933 (filed Jun. 6, 2011), 61/501,133 (filed Jun.24, 2011), and 61/537,998 (filed Sep. 22, 2011), the contents of each ofwhich are hereby incorporated in their entirety.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted in ASCII format via EFS-Web and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Aug. 10, 2016, isnamed A-1650-US—NP_SEQ_LIST_2094_08 10 2016. txt and is 1,661 KB insize.

FIELD OF THE INVENTION

The present disclosure relates to nucleic acid molecules encodingantigen binding proteins that bind to a complex comprising β-Klotho andat least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, includingantigen binding proteins that induce FGF21-like signaling, as well aspharmaceutical compositions comprising antigen binding proteins thatbind to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c, including antigen binding proteins thatinduce FGF21-like signaling, and methods for treating metabolicdisorders using such nucleic acids, polypeptides, or pharmaceuticalcompositions. Diagnostic methods using the antigen binding proteins arealso provided.

BACKGROUND

Fibroblast Growth Factor 21 (FGF21) is a secreted polypeptide thatbelongs to a subfamily of Fibroblast Growth Factors (FGFs) that includesFGF19, FGF21, and FGF23 (Itoh et al., (2004) Trend Genet. 20:563-69).FGF21 is an atypical FGF in that it is heparin independent and functionsas a hormone in the regulation of glucose, lipid, and energy metabolism.

It is highly expressed in liver and pancreas and is the only member ofthe FGF family to be primarily expressed in liver. Transgenic miceoverexpressing FGF21 exhibit metabolic phenotypes of slow growth rate,low plasma glucose and triglyceride levels, and an absence ofage-associated type 2 diabetes, islet hyperplasia, and obesity.Pharmacological administration of recombinant FGF21 protein in rodentand primate models results in normalized levels of plasma glucose,reduced triglyceride and cholesterol levels, and improved glucosetolerance and insulin sensitivity. In addition, FGF21 reduces bodyweight and body fat by increasing energy expenditure, physical activity,and metabolic rate. Experimental research provides support for thepharmacological administration of FGF21 for the treatment of type 2diabetes, obesity, dyslipidemia, and other metabolic conditions ordisorders in humans.

FGF21 is a liver derived endocrine hormone that stimulates glucoseuptake in adipocytes and lipid homeostasis through the activation of itsreceptor. Interestingly, in addition to the canonical FGF receptor, theFGF21 receptor also comprises the membrane associated β-Klotho as anessential cofactor. Activation of the FGF21 receptor leads to multipleeffects on a variety of metabolic parameters.

In mammals, FGFs mediate their action via a set of four FGF receptors,FGFR1-4, that in turn are expressed in multiple spliced variants, e.g.,FGFR1c, FGFR2c, FGFR3c and FGFR4. Each FGF receptor contains anintracellular tyrosine kinase domain that is activated upon ligandbinding, leading to downstream signaling pathways involving MAPKs(Erk1/2), RAF1, AKT1 and STATs. (Kharitonenkov et al., (2008) BioDrugs22:37-44). Several reports suggested that the “c”-reporter splicevariants of FGFR1-3 exhibit specific affinity to β-Klotho and could actas endogenous receptor for FGF21 (Kurosu et al., (2007) 1 Biol. Chem.282:26687-95); Ogawa et al., (2007) Proc. Natl. Acad. Sci. USA104:7432-37); Kharitonenkov et al., (2008) J. Cell Physiol. 215:1-7). Inthe liver, which abundantly expresses both β-Klotho and FGFR4, FGF21does not induce phosphorylation of MAPK albeit the strong binding ofFGF21 to the β-Klotho-FGFR4 complex. In 3T3-L1 cells and white adiposetissue, FGFR1 is by far the most abundant receptor, and it is thereforemost likely that FGF21's main functional receptors in this tissue arethe β-Klotho/FGFR1c complexes.

The present disclosure provides a human (or humanized) antigen bindingprotein, such as a monoclonal antibody, that induces FGF21-likesignaling, e.g., an agonistic antibody that mimics the function ofFGF21. Such an antibody is a molecule with FGF21-like activity andselectivity but with added therapeutically desirable characteristicstypical for an antibody such as protein stability, lack ofimmunogenicity, ease of production and long half-life in vivo.

SUMMARY

The instant disclosure provides antigen binding proteins that bind acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c, including antigen binding proteins that induceFGF21-like signaling, as well as pharmaceutical compositions comprisingantigen binding proteins that bind to a complex comprising β-Klotho andat least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, includingantigen binding proteins that induce FGF21-like signaling. In anotheraspect, also provided are expression vectors and host cells transformedor transfected with the expression vectors that comprise theaforementioned isolated nucleic acid molecules that encode the antigenbinding proteins disclosed herein. Representative heavy and light chainsare provided in Tables 1A and 1B; representative variable region heavychain and light chain sequences are provided in Tables 2A and 2B; codingsequences for the variable region of the heavy and light chains areprovided in Tables 2C and 2D; Tables 3A and 3B provide CDR regions ofthe disclosed variable heavy and light chains, and Tables 3C and 3Dprovide coding sequences for the disclosed CDRs.

In another aspect, also provided are methods of preparing antigenbinding proteins that specifically or selectively bind a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c and comprise the step of preparing the antigen bindingprotein from a host cell that secretes the antigen binding protein.

Other embodiments provide a method of preventing or treating a conditionin a subject in need of such treatment comprising administering atherapeutically effective amount of a pharmaceutical compositionprovided herein to a subject, wherein the condition is treatable bylowering blood glucose, insulin or serum lipid levels. In embodiments,the condition is type 2 diabetes, obesity, dyslipidemia, NASH,cardiovascular disease or metabolic syndrome.

These and other aspects are described in greater detail herein. Each ofthe aspects provided can encompass various embodiments provided herein.It is therefore anticipated that each of the embodiments involving oneelement or combinations of elements can be included in each aspectdescribed, and all such combinations of the above aspects andembodiments are expressly considered. Other features, objects, andadvantages of the disclosed antigen binding proteins and associatedmethods and compositions are apparent in the detailed description thatfollows.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1a-1b is an alignment showing the sequence homology between humanFGFR1c (GenBank Accession No P11362; SEQ ID NO: 4) and murine FGFR1c(GenBank Accession No NP 034336; SEQ ID NO: 1832); various features arehighlighted, including the signal peptide, transmembrane sequence,heparin binding region, and a consensus sequence (SEQ ID NO: 1833) isprovided.

FIG. 2a-2c is an alignment showing the sequence homology between humanβ-Klotho (GenBank Accession No NP_783864; SEQ ID NO: 7) and murineβ-Klotho (GenBank Accession No NP_112457; SEQ ID NO: 10); variousfeatures are highlighted, including the transmembrane sequence and twoglycosyl hydrolase domains, and a consensus sequence (SEQ ID NO: 1834)is provided.

FIG. 3 is a plot showing the representative data from Luciferasereporter activity screens of the antibodies disclosed herein with FGF21and a reference antibody 16H7.1 as positive controls (insert); thesehybridomas were generated by immunization with cell-bound receptor of293T transfectants expressing full length human β-Klotho and anN-terminal truncated form of human FGFR1c encompassing amino acidresidue #141 to #822 polypeptide of SEQ ID NO:4. X- and Y-axis in theplot are % FGF21 activity from two independent assays (n=1 and n=2) ofthe same set of hybridoma samples (gray circles) showing the consistencyof the assays; several hybridoma samples were also included as negativecontrols (black circles);

FIG. 4 shows a schematic representation of the chimeras constructed inrelation to present invention.

FIG. 5 shows the ability of the antigen binding proteins, as well ashuman FGF21, to activate chimeras in L6 cells.

FIGS. 6a-e show the amino acid alignment of heavy and light chains ofthe antibodies compared to the corresponding germline V-gene sequence.

DETAILED DESCRIPTION

The section headings used herein are for organizational purposes onlyand are not to be construed as limiting the subject matter described.

Unless otherwise defined herein, scientific and technical terms used inconnection with the present application shall have the meanings that arecommonly understood by those of ordinary skill in the art. Further,unless otherwise required by context, singular terms shall includepluralities and plural terms shall include the singular.

Generally, nomenclatures used in connection with, and techniques of,cell and tissue culture, molecular biology, immunology, microbiology,genetics and protein and nucleic acid chemistry and hybridizationdescribed herein are those well known and commonly used in the art. Themethods and techniques of the present application are generallyperformed according to conventional methods well known in the art and asdescribed in various general and more specific references that are citedand discussed throughout the present specification unless otherwiseindicated. See, e.g., Sambrook et al., Molecular Cloning: A LaboratoryManual, 3^(rd) ed., Cold Spring Harbor Laboratory Press, Cold SpringHarbor, N.Y. (2001) and subsequent editions, Ausubel et al., CurrentProtocols in Molecular Biology, Greene Publishing Associates (1992), andHarlow & Lane, Antibodies: A Laboratory Manual, Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y. (1988), which areincorporated herein by reference. Enzymatic reactions and purificationtechniques are performed according to manufacturer's specifications, ascommonly accomplished in the art or as described herein. The terminologyused in connection with, and the laboratory procedures and techniquesof, analytical chemistry, synthetic organic chemistry, and medicinal andpharmaceutical chemistry described herein are those well known andcommonly used in the art. Standard techniques can be used for chemicalsyntheses, chemical analyses, pharmaceutical preparation, formulation,and delivery, and treatment of patients.

It should be understood that the instant disclosure is not limited tothe particular methodology, protocols, and reagents, etc., describedherein and as such can vary. The terminology used herein is for thepurpose of describing particular embodiments only, and is not intendedto limit the scope of the present disclosure.

Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients or reaction conditions usedherein should be understood as modified in all instances by the term“about.” The term “about” when used in connection with percentages canmean±5%, e.g., 1%, 2%, 3%, or 4%.

I. Definitions

As used herein, the terms “a” and “an” mean “one or more” unlessspecifically stated otherwise.

As used herein, an “antigen binding protein” is a protein comprising aportion that binds to an antigen or target and, optionally, a scaffoldor framework portion that allows the antigen binding portion to adopt aconformation that promotes binding of the antigen binding protein to theantigen. Examples of antigen binding proteins include a human antibody,a humanized antibody; a chimeric antibody; a recombinant antibody; asingle chain antibody; a diabody; a triabody; a tetrabody; a Fabfragment; a F(ab′)₂ fragment; an IgD antibody; an IgE antibody; an IgMantibody; an IgG1 antibody; an IgG2 antibody; an IgG3 antibody; or anIgG4 antibody, and fragments thereof. The antigen binding protein cancomprise, for example, an alternative protein scaffold or artificialscaffold with grafted CDRs or CDR derivatives. Such scaffolds include,but are not limited to, antibody-derived scaffolds comprising mutationsintroduced to, for example, stabilize the three-dimensional structure ofthe antigen binding protein as well as wholly synthetic scaffoldscomprising, for example, a biocompatible polymer. See, e.g., Korndorferet al., (2003) Proteins: Structure, Function, and Bioinformatics,53(1):121-129; Roque et al., (2004) Biotechnol. Prog. 20:639-654. Inaddition, peptide antibody mimetics (“PAMs”) can be used, as well asscaffolds based on antibody mimetics utilizing fibronectin components asa scaffold.

An antigen binding protein can have, for example, the structure of anaturally occurring immunoglobulin. An “immunoglobulin” is a tetramericmolecule. In a naturally occurring immunoglobulin, each tetramer iscomposed of two identical pairs of polypeptide chains, each pair havingone “light” (about 25 kDa) and one “heavy” chain (about 50-70 kDa). Theamino-terminal portion of each chain includes a variable region of about100 to 110 or more amino acids primarily responsible for antigenrecognition. The carboxy-terminal portion of each chain defines aconstant region primarily responsible for effector function. Human lightchains are classified as kappa and lambda light chains. Heavy chains areclassified as mu, delta, gamma, alpha, or epsilon, and define theantibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Withinlight and heavy chains, the variable and constant regions are joined bya “J” region of about 12 or more amino acids, with the heavy chain alsoincluding a “D” region of about 10 more amino acids. See generally,Fundamental Immunology 2^(nd) ed. Ch. 7 (Paul, W., ed., Raven Press,N.Y. (1989)), incorporated by reference in its entirety for allpurposes. The variable regions of each light/heavy chain pair form theantibody binding site such that an intact immunoglobulin has two bindingsites.

Naturally occurring immunoglobulin chains exhibit the same generalstructure of relatively conserved framework regions (FR) joined by threehypervariable regions, also called complementarity determining regionsor CDRs. From N-terminus to C-terminus, both light and heavy chainscomprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. Theassignment of amino acids to each domain can be done in accordance withthe definitions of Kabat et al., (1991) “Sequences of Proteins ofImmunological Interest”, 5^(th) Ed., US Dept. of Health and HumanServices, PHS, NIH, NIH Publication no. 91-3242. Although presentedherein using the Kabat nomenclature system, as desired, the CDRsdisclosed herein can also be redefined according an alternativenomenclature scheme, such as that of Chothia (see Chothia & Lesk, (1987)J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature 342:878-883 orHonegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670).

In the context of the instant disclosure an antigen binding protein issaid to “specifically bind” or “selectively bind” its target antigenwhen the dissociation constant (K_(D)) is ≦10⁻⁸ M. The antibodyspecifically binds antigen with “high affinity” when the K_(D) is≦5×10⁻⁹ M, and with “very high affinity” when the K_(D) is ≦5×10⁻¹⁰ M.In one embodiment, the antibodies will bind to a complex comprisingβ-Klotho and an FGFR, including a complex comprising both human FGFR1cand human β-Klotho, with a K_(D) of between about 10⁻⁷ M and 10⁻¹² M,and in yet another embodiment the antibodies will bind with aK_(D)≦5×10⁻⁹.

An “antibody” refers to an intact immunoglobulin or to an antigenbinding portion thereof that competes with the intact antibody forspecific binding, unless otherwise specified. Antigen binding portionscan be produced by recombinant DNA techniques or by enzymatic orchemical cleavage of intact antibodies. Antigen binding portionsinclude, inter alia, Fab, Fab′, F(ab′)₂, Fv, domain antibodies (dAbs),fragments including complementarity determining regions (CDRs),single-chain antibodies (scFv), chimeric antibodies, diabodies,triabodies, tetrabodies, and polypeptides that contain at least aportion of an immunoglobulin that is sufficient to confer specificantigen binding to the polypeptide.

A Fab fragment is a monovalent fragment having the V_(L), V_(H), C_(L)and C_(H)1 domains; a F(ab′)₂ fragment is a bivalent fragment having twoFab fragments linked by a disulfide bridge at the hinge region; a Fdfragment has the V_(H) and C_(H)1 domains; an Fv fragment has the V_(L)and V_(H) domains of a single arm of an antibody; and a dAb fragment hasa V_(H) domain, a V_(L) domain, or an antigen-binding fragment of aV_(H) or V_(L) domain (U.S. Pat. Nos. 6,846,634, and 6,696,245; and USApp. Pub. Nos. 05/0202512, 04/0202995, 04/0038291, 04/0009507,03/0039958, Ward et al., Nature 341:544-546 (1989)).

A single-chain antibody (scFv) is an antibody in which a V_(L) and aV_(H) region are joined via a linker (e.g., a synthetic sequence ofamino acid residues) to form a continuous protein chain wherein thelinker is long enough to allow the protein chain to fold back on itselfand form a monovalent antigen binding site (see, e.g., Bird et al.,(1988) Science 242:423-26 and Huston et al., (1988) Proc. Natl. Acad.Sci. USA 85:5879-83). Diabodies are bivalent antibodies comprising twopolypeptide chains, wherein each polypeptide chain comprises V_(H) andV_(L) domains joined by a linker that is too short to allow for pairingbetween two domains on the same chain, thus allowing each domain to pairwith a complementary domain on another polypeptide chain (see, e.g.,Holliger et al., (1993) Proc. Natl. Acad. Sci. USA 90:6444-48, andPoljak et al., (1994) Structure 2:1121-23). If the two polypeptidechains of a diabody are identical, then a diabody resulting from theirpairing will have two identical antigen binding sites. Polypeptidechains having different sequences can be used to make a diabody with twodifferent antigen binding sites. Similarly, tribodies and tetrabodiesare antibodies comprising three and four polypeptide chains,respectively, and forming three and four antigen binding sites,respectively, which can be the same or different.

Complementarity determining regions (CDRs) and framework regions (FR) ofa given antibody can be identified using the system described by Kabatet al., (1991) “Sequences of Proteins of Immunological Interest”, 5^(th)Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publicationno. 91-3242. Although presented using the Kabat nomenclature system, asdesired, the CDRs disclosed herein can also be redefined according analternative nomenclature scheme, such as that of Chothia (see Chothia &Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature342:878-883 or Honegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670).One or more CDRs can be incorporated into a molecule either covalentlyor noncovalently to make it an antigen binding protein. An antigenbinding protein can incorporate the CDR(s) as part of a largerpolypeptide chain, can covalently link the CDR(s) to another polypeptidechain, or can incorporate the CDR(s) noncovalently. The CDRs permit theantigen binding protein to specifically bind to a particular antigen ofinterest.

An antigen binding protein can but need not have one or more bindingsites. If there is more than one binding site, the binding sites can beidentical to one another or can be different. For example, a naturallyoccurring human immunoglobulin typically has two identical bindingsites, while a “bispecific” or “bifunctional” antibody has two differentbinding sites. Antigen binding proteins of this bispecific form (e.g.,those comprising various heavy and light chain CDRs provided herein)comprise aspects of the instant disclosure.

The term “human antibody” includes all antibodies that have one or morevariable and constant regions derived from human immunoglobulinsequences. In one embodiment, all of the variable and constant domainsare derived from human immunoglobulin sequences (a fully humanantibody). These antibodies can be prepared in a variety of ways,examples of which are described below, including through theimmunization with an antigen of interest of a mouse that is geneticallymodified to express antibodies derived from human heavy and/or lightchain-encoding genes, such as a mouse derived from a XENOMOUSE®,ULTIMAB™, HUMAB-MOUSE®, VELOCIMOUSE®, VELOCIMMUNE®, KYMOUSE, or ALIVAMABsystem, or derived from human heavy chain transgenic mouse, transgenicrat human antibody repertoire, transgenic rabbit human antibodyrepertoire or cow human antibody repertoire or HUTARG™ technology.Phage-based approaches can also be employed.

A humanized antibody has a sequence that differs from the sequence of anantibody derived from a non-human species by one or more amino acidsubstitutions, deletions, and/or additions, such that the humanizedantibody is less likely to induce an immune response, and/or induces aless severe immune response, as compared to the non-human speciesantibody, when it is administered to a human subject. In one embodiment,certain amino acids in the framework and constant domains of the heavyand/or light chains of the non-human species antibody are mutated toproduce the humanized antibody. In another embodiment, the constantdomain(s) from a human antibody are fused to the variable domain(s) of anon-human species. In another embodiment, one or more amino acidresidues in one or more CDR sequences of a non-human antibody arechanged to reduce the likely immunogenicity of the non-human antibodywhen it is administered to a human subject, wherein the changed aminoacid residues either are not critical for immunospecific binding of theantibody to its antigen, or the changes to the amino acid sequence thatare made are conservative changes, such that the binding of thehumanized antibody to the antigen is not significantly worse than thebinding of the non-human antibody to the antigen. Examples of how tomake humanized antibodies can be found in U.S. Pat. Nos. 6,054,297,5,886,152 and 5,877,293.

The term “chimeric antibody” refers to an antibody that contains one ormore regions from one antibody and one or more regions from one or moreother antibodies. In one embodiment, one or more of the CDRs are derivedfrom a human antibody that binds to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In anotherembodiment, all of the CDRs are derived from a human antibody that bindsto a complex β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c. In another embodiment, the CDRs from more than one humanantibody that binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are mixed and matched in achimeric antibody. For instance, a chimeric antibody can comprise a CDR1from the light chain of a first human antibody that binds to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c, a CDR2 and a CDR3 from the light chain of a second humanantibody that binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, and the CDRs from the heavychain from a third antibody that binds to a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Further,the framework regions can be derived from one of the same antibodiesthat bind to a complex comprising β-Klotho and at least one of (i)FGFR1c, (ii) FGFR2c and (iii) FGFR3c, from one or more differentantibodies, such as a human antibody, or from a humanized antibody. Inone example of a chimeric antibody, a portion of the heavy and/or lightchain is identical with, homologous to, or derived from an antibody froma particular species or belonging to a particular antibody class orsubclass, while the remainder of the chain(s) is/are identical with,homologous to, or derived from an antibody or antibodies from anotherspecies or belonging to another antibody class or subclass. Alsoincluded are fragments of such antibodies that exhibit the desiredbiological activity (e.g., the ability to specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c).

The term “light chain” includes a full-length light chain and fragmentsthereof having sufficient variable region sequence to confer bindingspecificity. A full-length light chain includes a variable regiondomain, V_(L), and a constant region domain, C_(L). The variable regiondomain of the light chain is at the amino-terminus of the polypeptide.Light chains include kappa (“κ”) chains and lambda (“λ”) chains.

The term “heavy chain” includes a full-length heavy chain and fragmentsthereof having sufficient variable region sequence to confer bindingspecificity. A full-length heavy chain includes a variable regiondomain, V_(H), and three constant region domains, C_(H)1, C_(H)2, andC_(H)3. The V_(H) domain is at the amino-terminus of the polypeptide,and the C_(H) domains are at the carboxyl-terminus, with the C_(H)3being closest to the carboxy-terminus of the polypeptide. Heavy chainscan be of any isotype, including IgG (including IgG1, IgG2, IgG3 andIgG4 subtypes), IgA (including IgA1 and IgA2 subtypes), IgM and IgE.

The term “immunologically functional fragment” (or simply “fragment”) ofan antigen binding protein, e.g., an antibody or immunoglobulin chain(heavy or light chain), as used herein, is an antigen binding proteincomprising a portion (regardless of how that portion is obtained orsynthesized) of an antibody that lacks at least some of the amino acidspresent in a full-length chain but which is capable of specificallybinding to an antigen. Such fragments are biologically active in thatthey bind specifically to the target antigen and can compete with otherantigen binding proteins, including intact antibodies, for specificbinding to a given epitope. In one aspect, such a fragment will retainat least one CDR present in the full-length light or heavy chain, and insome embodiments will comprise a single heavy chain and/or light chainor portion thereof. These biologically active fragments can be producedby recombinant DNA techniques, or can be produced by enzymatic orchemical cleavage of antigen binding proteins, including intactantibodies. Immunologically functional immunoglobulin fragments include,but are not limited to, Fab, Fab′, F(ab′)₂, Fv, domain antibodies andsingle-chain antibodies, and can be derived from any mammalian source,including but not limited to human, mouse, rat, camelid or rabbit. It iscontemplated further that a functional portion of the antigen bindingproteins disclosed herein, for example, one or more CDRs, could becovalently bound to a second protein or to a small molecule to create atherapeutic agent directed to a particular target in the body,possessing bifunctional therapeutic properties, or having a prolongedserum half-life.

An “Fc” region contains two heavy chain fragments comprising the C_(H)2and C_(H)3 domains of an antibody. The two heavy chain fragments areheld together by two or more disulfide bonds and by hydrophobicinteractions of the C_(H)3 domains.

An “Fab′ fragment” contains one light chain and a portion of one heavychain that contains the V_(H) domain and the C_(H)1 domain and also theregion between the C_(H)1 and C_(H)2 domains, such that an interchaindisulfide bond can be formed between the two heavy chains of two Fab′fragments to form an F(ab′)₂ molecule.

An “F(ab′)₂ fragment” contains two light chains and two heavy chainscontaining a portion of the constant region between the C_(H)1 andC_(H)2 domains, such that an interchain disulfide bond is formed betweenthe two heavy chains. A F(ab′)₂ fragment thus is composed of two Fab′fragments that are held together by a disulfide bond between the twoheavy chains.

The “Fv region” comprises the variable regions from both the heavy andlight chains, but lacks the constant regions.

A “domain antibody” is an immunologically functional immunoglobulinfragment containing only the variable region of a heavy chain or thevariable region of a light chain. In some instances, two or more V_(H)regions are covalently joined with a peptide linker to create a bivalentdomain antibody. The two V_(H) regions of a bivalent domain antibody cantarget the same or different antigens.

A “hemibody” is an immunologically-functional immunoglobulin constructcomprising a complete heavy chain, a complete light chain and a secondheavy chain Fc region paired with the Fc region of the complete heavychain. A linker can, but need not, be employed to join the heavy chainFc region and the second heavy chain Fc region. In particularembodiments a hemibody is a monovalent form of an antigen bindingprotein disclosed herein. In other embodiments, pairs of chargedresidues can be employed to associate one Fc region with the second Fcregion.

A “bivalent antigen binding protein” or “bivalent antibody” comprisestwo antigen binding sites. In some instances, the two binding sites havethe same antigen specificities. Bivalent antigen binding proteins andbivalent antibodies can be bispecific, as described herein, and formaspects of the instant disclosure.

A “multispecific antigen binding protein” or “multispecific antibody” isone that targets more than one antigen or epitope, and forms anotheraspect of the instant disclosure.

A “bispecific,” “dual-specific” or “bifunctional” antigen bindingprotein or antibody is a hybrid antigen binding protein or antibody,respectively, having two different antigen binding sites. Bispecificantigen binding proteins and antibodies are a species of multispecificantigen binding protein or multispecific antibody and can be produced bya variety of methods including, but not limited to, fusion of hybridomasor linking of Fab′ fragments. See, e.g., Songsivilai and Lachmann,(1990) Clin. Exp. Immunol. 79:315-321; Kostelny et al., (1992) J.Immunol. 148:1547-1553. The two binding sites of a bispecific antigenbinding protein or antibody will bind to two different epitopes, whichcan reside on the same (e.g., β-Klotho, FGFR1c, FGFR2c, or FGFR3c) ordifferent protein targets (e.g., β-Klotho and one of (i) FGFR1c, (ii)FGFR2c, and (iii) FGFR3c).

The terms “FGF21-like signaling” and “induces FGF21-like signaling,”when applied to an antigen binding protein of the present disclosure,means that the antigen binding protein mimics, or modulates, an in vivobiological effect induced by the binding to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cand induces a biological response that otherwise would result from FGF21binding to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c in vivo. In assessing the binding andspecificity of an antigen binding protein, e.g., an antibody orimmunologically functional fragment thereof, an antibody or fragment isdeemed to induce a biological response when the response is equal to orgreater than 5%, and preferably equal to or greater than 10%, 15%, 20%,25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or95%, of the activity of a wild type FGF21 standard comprising the matureform of SEQ ID NO: 2 (i.e., the mature form of the human FGF21 sequence)and has the following properties: exhibiting an efficacy level of equalto or more than 5% of an FGF21 standard, with an EC₅₀ of equal to orless than 100 nM, e.g., 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM,20 nM or 10 nM in (1) the recombinant FGF21 receptor-mediated luciferasereporter cell assay of Example 4; (2) ERK-phosphorylation in therecombinant FGF21 receptor mediated cell assay of Example 4; and (3)ERK-phosphorylation in human adipocytes as described in Example 4. The“potency” of an antigen binding protein is defined as exhibiting an EC50of equal to or less than 100 nM, e.g., 90 nM, 80 nM, 70 nM, 60 nM, 50nM, 40 nM, 30 nM, 20 nM, 10 nM and preferably less than 10 nM of theantigen binding protein in the following assays: (1) the recombinantFGF21 receptor mediated luciferase-reporter cell assay of Example 4; (2)the ERK-phosphorylation in the recombinant FGF21 receptor mediated cellassay of Example 4; and (3) ERK-phosphorylation in human adipocytes asdescribed in Example 4.

It is noted that not all of the antigen binding proteins of the presentdisclosure induce FGF21-mediated signaling (e.g., that induce agonisticactivity), nor is this property desirable in all circumstances.Nevertheless, antigen binding proteins that do not induce FGF21-mediatedsignaling form aspects of the present disclosure and may be useful asdiagnostic reagents or other applications.

As used herein, the term “FGF21R” means a multimeric receptor complexthat FGF21 is known or suspected to form in vivo. In variousembodiments, FGF21R comprises (i) an FGFR, e.g., FGFR1c, FGFR2c, FGFR3cor FGFR4, and (ii) β-Klotho.

The term “polynucleotide” or “nucleic acid” includes bothsingle-stranded and double-stranded nucleotide polymers. The nucleotidescomprising the polynucleotide can be ribonucleotides ordeoxyribonucleotides or a modified form of either type of nucleotide.Said modifications include base modifications such as bromouridine andinosine derivatives, ribose modifications such as 2′, 3′-dideoxyribose,and internucleotide linkage modifications such as phosphorothioate,phosphorodithioate, phosphoroselenoate, phosphorodiselenoate,phosphoroanilothioate, phoshoraniladate and phosphoroamidate.

The term “oligonucleotide” means a polynucleotide comprising 200 orfewer nucleotides. In some embodiments, oligonucleotides are 10 to 60bases in length. In other embodiments, oligonucleotides are 12, 13, 14,15, 16, 17, 18, 19, or 20 to 40 nucleotides in length. Oligonucleotidescan be single stranded or double stranded, e.g., for use in theconstruction of a mutant gene. Oligonucleotides can be sense orantisense oligonucleotides. An oligonucleotide can include a label,including a radiolabel, a fluorescent label, a hapten or an antigeniclabel, for detection assays. Oligonucleotides can be used, for example,as PCR primers, cloning primers or hybridization probes.

An “isolated nucleic acid molecule” means a DNA or RNA of genomic, mRNA,cDNA, or synthetic origin or some combination thereof which is notassociated with all or a portion of a polynucleotide in which theisolated polynucleotide is found in nature, or is linked to apolynucleotide to which it is not linked in nature. For purposes of thisdisclosure, it is understood that “a nucleic acid molecule comprising” aparticular nucleotide sequence does not encompass intact chromosomes.Isolated nucleic acid molecules “comprising” specified nucleic acidsequences can include, in addition to the specified sequences, codingsequences for up to ten or even up to twenty other proteins or portionsthereof, or can include operably linked regulatory sequences thatcontrol expression of the coding region of the recited nucleic acidsequences, and/or can include vector sequences.

Unless specified otherwise, the left-hand end of any single-strandedpolynucleotide sequence discussed herein is the 5′ end; the left-handdirection of double-stranded polynucleotide sequences is referred to asthe 5′ direction. The direction of 5′ to 3′ addition of nascent RNAtranscripts is referred to as the transcription direction; sequenceregions on the DNA strand having the same sequence as the RNA transcriptthat are 5′ to the 5′ end of the RNA transcript are referred to as“upstream sequences;” sequence regions on the DNA strand having the samesequence as the RNA transcript that are 3′ to the 3′ end of the RNAtranscript are referred to as “downstream sequences.”

The term “control sequence” refers to a polynucleotide sequence that canaffect the expression and processing of coding sequences to which it isligated. The nature of such control sequences can depend upon the hostorganism. In particular embodiments, control sequences for prokaryotescan include a promoter, a ribosomal binding site, and a transcriptiontermination sequence. For example, control sequences for eukaryotes caninclude promoters comprising one or a plurality of recognition sites fortranscription factors, transcription enhancer sequences, andtranscription termination sequence. “Control sequences” can includeleader sequences and/or fusion partner sequences.

The term “vector” means any molecule or entity (e.g., nucleic acid,plasmid, bacteriophage or virus) used to transfer protein codinginformation into a host cell.

The term “expression vector” or “expression construct” refers to avector that is suitable for transformation of a host cell and containsnucleic acid sequences that direct and/or control (in conjunction withthe host cell) expression of one or more heterologous coding regionsoperatively linked thereto. An expression construct can include, but isnot limited to, sequences that affect or control transcription,translation, and, if introns are present, affect RNA splicing of acoding region operably linked thereto.

As used herein, “operably linked” means that the components to which theterm is applied are in a relationship that allows them to carry outtheir inherent functions under suitable conditions. For example, acontrol sequence in a vector that is “operably linked” to a proteincoding sequence is ligated thereto so that expression of the proteincoding sequence is achieved under conditions compatible with thetranscriptional activity of the control sequences.

The term “host cell” means a cell that has been transformed, or iscapable of being transformed, with a nucleic acid sequence and therebyexpresses a gene of interest. The term includes the progeny of theparent cell, whether or not the progeny is identical in morphology or ingenetic make-up to the original parent cell, so long as the gene ofinterest is present.

The term “transduction” means the transfer of genes from one bacteriumto another, usually by bacteriophage. “Transduction” also refers to theacquisition and transfer of eukaryotic cellular sequences byreplication-defective retroviruses.

The term “transfection” means the uptake of foreign or exogenous DNA bya cell, and a cell has been “transfected” when the exogenous DNA hasbeen introduced inside the cell membrane. A number of transfectiontechniques are well known in the art and are disclosed herein. See,e.g., Graham et al., (1973) Virology 52:456; Sambrook et al., (2001),supra; Davis et al., (1986) Basic Methods in Molecular Biology,Elsevier; Chu et al., (1981) Gene 13:197. Such techniques can be used tointroduce one or more exogenous DNA moieties into suitable host cells.

The term “transformation” refers to a change in a cell's geneticcharacteristics, and a cell has been transformed when it has beenmodified to contain new DNA or RNA. For example, a cell is transformedwhere it is genetically modified from its native state by introducingnew genetic material via transfection, transduction, or othertechniques. Following transfection or transduction, the transforming DNAcan recombine with that of the cell by physically integrating into achromosome of the cell, or can be maintained transiently as an episomalelement without being replicated, or can replicate independently as aplasmid. A cell is considered to have been “stably transformed” when thetransforming DNA is replicated with the division of the cell.

The terms “polypeptide” or “protein” are used interchangeably herein torefer to a polymer of amino acid residues. The terms also apply to aminoacid polymers in which one or more amino acid residues is an analog ormimetic of a corresponding naturally occurring amino acid, as well as tonaturally occurring amino acid polymers. The terms can also encompassamino acid polymers that have been modified, e.g., by the addition ofcarbohydrate residues to form glycoproteins, or phosphorylated.Polypeptides and proteins can be produced by a naturally-occurring andnon-recombinant cell, or polypeptides and proteins can be produced by agenetically-engineered or recombinant cell. Polypeptides and proteinscan comprise molecules having the amino acid sequence of a nativeprotein, or molecules having deletions from, additions to, and/orsubstitutions of one or more amino acids of the native sequence. Theterms “polypeptide” and “protein” encompass antigen binding proteinsthat specifically or selectively bind to a complex comprising β-Klothoand an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c), or sequences that havedeletions from, additions to, and/or substitutions of one or more aminoacids of an antigen binding protein that specifically or selectivelybinds to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c. The term “polypeptide fragment” refers toa polypeptide that has an amino-terminal deletion, a carboxyl-terminaldeletion, and/or an internal deletion as compared with the full-lengthprotein. Such fragments can also contain modified amino acids ascompared with the full-length protein. In certain embodiments, fragmentsare about five to 500 amino acids long. For example, fragments can be atleast 5, 6, 8, 10, 14, 20, 50, 70, 100, 110, 150, 200, 250, 300, 350,400, or 450 amino acids long. Useful polypeptide fragments includeimmunologically functional fragments of antibodies, including bindingdomains. In the case of an antigen binding protein that binds to acomplex β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii)FGFR3c, useful fragments include but are not limited to a CDR region, avariable domain of a heavy or light chain, a portion of an antibodychain or just its variable region including two CDRs, and the like.

The term “isolated protein” referred means that a subject protein (1) isfree of at least some other proteins with which it would normally befound, (2) is essentially free of other proteins from the same source,e.g., from the same species, (3) is expressed by a cell from a differentspecies, (4) has been separated from at least about 50 percent ofpolynucleotides, lipids, carbohydrates, or other materials with which itis associated in nature, (5) is operably associated (by covalent ornoncovalent interaction) with a polypeptide with which it is notassociated in nature, or (6) does not occur in nature. Typically, an“isolated protein” constitutes at least about 5%, at least about 10%, atleast about 25%, or at least about 50% of a given sample. Genomic DNA,cDNA, mRNA or other RNA, of synthetic origin, or any combination thereofcan encode such an isolated protein. Preferably, the isolated protein issubstantially free from proteins or polypeptides or other contaminantsthat are found in its natural environment that would interfere with itstherapeutic, diagnostic, prophylactic, research or other use.

A “variant” of a polypeptide (e.g., an antigen binding protein, or anantibody) comprises an amino acid sequence wherein one or more aminoacid residues are inserted into, deleted from and/or substituted intothe amino acid sequence relative to another polypeptide sequence.Variants include fusion proteins.

A “derivative” of a polypeptide is a polypeptide (e.g., an antigenbinding protein, or an antibody) that has been chemically modified insome manner distinct from insertion, deletion, or substitution variants,e.g., by conjugation to another chemical moiety.

The term “naturally occurring” as used throughout the specification inconnection with biological materials such as polypeptides, nucleicacids, host cells, and the like, refers to materials which are found innature.

“Antigen binding region” means a protein, or a portion of a protein,that specifically binds a specified antigen, e.g., a complex comprisingβ-Klotho and an β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c. For example, that portion of an antigen binding proteinthat contains the amino acid residues that interact with an antigen andconfer on the antigen binding protein its specificity and affinity forthe antigen is referred to as “antigen binding region.” An antigenbinding region typically includes one or more “complementary bindingregions” (“CDRs”). Certain antigen binding regions also include one ormore “framework” regions. A “CDR” is an amino acid sequence thatcontributes to antigen binding specificity and affinity. “Framework”regions can aid in maintaining the proper conformation of the CDRs topromote binding between the antigen binding region and an antigen.

In certain aspects, recombinant antigen binding proteins that bind to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c, are provided. In this context, a “recombinant protein”is a protein made using recombinant techniques, i.e., through theexpression of a recombinant nucleic acid as described herein. Methodsand techniques for the production of recombinant proteins are well knownin the art.

The term “compete” when used in the context of antigen binding proteins(e.g., neutralizing antigen binding proteins, neutralizing antibodies,agonistic antigen binding proteins, agonistic antibodies and bindingproteins that bind to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c) that compete for the sameepitope or binding site on a target means competition between antigenbinding proteins as determined by an assay in which the antigen bindingprotein (e.g., antibody or immunologically functional fragment thereof)under study prevents or inhibits the specific binding of a referencemolecule (e.g., a reference ligand, or reference antigen bindingprotein, such as a reference antibody) to a common antigen (e.g.,FGFR1c, FGFR2c, FGFR3c, β-Klotho or a fragment thereof, or a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c). Numerous types of competitive binding assays can be usedto determine if a test molecule competes with a reference molecule forbinding. Examples of assays that can be employed include solid phasedirect or indirect radioimmunoassay (RIA), solid phase direct orindirect enzyme immunoassay (EIA), sandwich competition assay (see,e.g., Stahli et al., (1983) Methods in Enzymology 9:242-253); solidphase direct biotin-avidin EIA (see, e.g., Kirkland et al., (1986) J.Immunol. 137:3614-3619) solid phase direct labeled assay, solid phasedirect labeled sandwich assay (see, e.g., Harlow and Lane, (1988)supra); solid phase direct label RIA using 1-125 label (see, e.g., Morelet al., (1988) Molec. Immunol. 25:7-15); solid phase directbiotin-avidin EIA (see, e.g., Cheung, et al., (1990) Virology176:546-552); and direct labeled RIA (Moldenhauer et al., (1990) Scand.J. Immunol. 32:77-82). Typically, such an assay involves the use of apurified antigen bound to a solid surface or cells bearing either of anunlabelled test antigen binding protein or a labeled reference antigenbinding protein. Competitive inhibition is measured by determining theamount of label bound to the solid surface or cells in the presence ofthe test antigen binding protein. Usually the test antigen bindingprotein is present in excess. Antigen binding proteins identified bycompetition assay (competing antigen binding proteins) include antigenbinding proteins binding to the same epitope as the reference antigenbinding proteins and antigen binding proteins binding to an adjacentepitope sufficiently proximal to the epitope bound by the referenceantigen binding protein for steric hindrance to occur. Additionaldetails regarding methods for determining competitive binding areprovided in the examples herein. Usually, when a competing antigenbinding protein is present in excess, it will inhibit specific bindingof a reference antigen binding protein to a common antigen by at least40%, 45%, 50%, 55%, 60%, 65%, 70% or 75%. In some instance, binding isinhibited by at least 80%, 85%, 90%, 95%, or 97% or more.

The term “antigen” refers to a molecule or a portion of a moleculecapable of being bound by a selective binding agent, such as an antigenbinding protein (including, e.g., an antibody or immunologicalfunctional fragment thereof), and may also be capable of being used inan animal to produce antibodies capable of binding to that antigen. Anantigen can possess one or more epitopes that are capable of interactingwith different antigen binding proteins, e.g., antibodies.

The term “epitope” means the amino acids of a target molecule that arecontacted by an antigen binding protein (for example, an antibody) whenthe antigen binding protein is bound to the target molecule. The termincludes any subset of the complete list of amino acids of the targetmolecule that are contacted when an antigen binding protein, such as anantibody, is bound to the target molecule. An epitope can be contiguousor non-contiguous (e.g., (i) in a single-chain polypeptide, amino acidresidues that are not contiguous to one another in the polypeptidesequence but that within in context of the target molecule are bound bythe antigen binding protein, or (ii) in a multimeric receptor comprisingtwo or more individual components, e.g., a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, amino acidresidues that are present on one or more of the individual components,but which are still bound by the antigen binding protein). In certainembodiments, epitopes can be mimetic in that they comprise a threedimensional structure that is similar to an antigenic epitope used togenerate the antigen binding protein, yet comprise none or only some ofthe amino acid residues found in that epitope used to generate theantigen binding protein. Most often, epitopes reside on proteins, but insome instances can reside on other kinds of molecules, such as nucleicacids. Epitope determinants can include chemically active surfacegroupings of molecules such as amino acids, sugar side chains,phosphoryl or sulfonyl groups, and can have specific three dimensionalstructural characteristics, and/or specific charge characteristics.Generally, antigen binding proteins specific for a particular targetmolecule will preferentially recognize an epitope on the target moleculein a complex mixture of proteins and/or macromolecules.

The term “identity” refers to a relationship between the sequences oftwo or more polypeptide molecules or two or more nucleic acid molecules,as determined by aligning and comparing the sequences. “Percentidentity” means the percent of identical residues between the aminoacids or nucleotides in the compared molecules and is calculated basedon the size of the smallest of the molecules being compared. For thesecalculations, gaps in alignments (if any) must be addressed by aparticular mathematical model or computer program (i.e., an“algorithm”). Methods that can be used to calculate the identity of thealigned nucleic acids or polypeptides include those described inComputational Molecular Biology, (Lesk, A. M., ed.), (1988) New York:Oxford University Press; Biocomputing Informatics and Genome Projects,(Smith, D. W., ed.), 1993, New York: Academic Press; Computer Analysisof Sequence Data, Part I, (Griffin, A. M., and Griffin, H. G., eds.),1994, New Jersey: Humana Press; von Heinje, G., (1987) Sequence Analysisin Molecular Biology, New York: Academic Press; Sequence AnalysisPrimer, (Gribskov, M. and Devereux, J., eds.), 1991, New York: M.Stockton Press; and Carillo et al., (1988) J. Applied Math. 48:1073.

In calculating percent identity, the sequences being compared arealigned in a way that gives the largest match between the sequences. Thecomputer program used to determine percent identity is the GCG programpackage, which includes GAP (Devereux et al., (1984) Nucl. Acid Res.12:387; Genetics Computer Group, University of Wisconsin, Madison,Wis.). The computer algorithm GAP is used to align the two polypeptidesor polynucleotides for which the percent sequence identity is to bedetermined. The sequences are aligned for optimal matching of theirrespective amino acid or nucleotide (the “matched span”, as determinedby the algorithm). A gap opening penalty (which is calculated as 3× theaverage diagonal, wherein the “average diagonal” is the average of thediagonal of the comparison matrix being used; the “diagonal” is thescore or number assigned to each perfect amino acid match by theparticular comparison matrix) and a gap extension penalty (which isusually 1/10 times the gap opening penalty), as well as a comparisonmatrix such as PAM 250 or BLOSUM 62 are used in conjunction with thealgorithm. In certain embodiments, a standard comparison matrix (see,Dayhoff et al., (1978) Atlas of Protein Sequence and Structure 5:345-352for the PAM 250 comparison matrix; Henikoff et al., (1992) Proc. Natl.Acad. Sci. U.S.A. 89:10915-10919 for the BLOSUM 62 comparison matrix) isalso used by the algorithm.

Recommended parameters for determining percent identity for polypeptidesor nucleotide sequences using the GAP program are the following:

Algorithm: Needleman et al., 1970, J. Mol. Biol. 48:443-453;

Comparison matrix: BLOSUM 62 from Henikoff et al., 1992, supra;

Gap Penalty: 12 (but with no penalty for end gaps)

Gap Length Penalty: 4

Threshold of Similarity: 0

Certain alignment schemes for aligning two amino acid sequences canresult in matching of only a short region of the two sequences, and thissmall aligned region can have very high sequence identity even thoughthere is no significant relationship between the two full-lengthsequences. Accordingly, the selected alignment method (e.g., the GAPprogram) can be adjusted if so desired to result in an alignment thatspans at least 50 contiguous amino acids of the target polypeptide.

As used herein, “substantially pure” means that the described species ofmolecule is the predominant species present, that is, on a molar basisit is more abundant than any other individual species in the samemixture. In certain embodiments, a substantially pure molecule is acomposition wherein the object species comprises at least 50% (on amolar basis) of all macromolecular species present. In otherembodiments, a substantially pure composition will comprise at least80%, 85%, 90%, 95%, or 99% of all macromolecular species present in thecomposition. In other embodiments, the object species is purified toessential homogeneity wherein contaminating species cannot be detectedin the composition by conventional detection methods and thus thecomposition consists of a single detectable macromolecular species.

The terms “treat” and “treating” refer to any indicia of success in thetreatment or amelioration of an injury, pathology or condition,including any objective or subjective parameter such as abatement;remission; diminishing of symptoms or making the injury, pathology orcondition more tolerable to the patient; slowing in the rate ofdegeneration or decline; making the final point of degeneration lessdebilitating; improving a patient's physical or mental well-being. Thetreatment or amelioration of symptoms can be based on objective orsubjective parameters; including the results of a physical examination,neuropsychiatric exams, and/or a psychiatric evaluation. For example,certain methods presented herein can be employed to treat Type 2diabetes, obesity and/or dyslipidemia, either prophylactically or as anacute treatment, to decrease plasma glucose levels, to decreasecirculating triglyceride levels, to decrease circulating cholesterollevels and/or ameliorate a symptom associated with type 2 diabetes,obesity and dyslipidemia.

An “effective amount” is generally an amount sufficient to reduce theseverity and/or frequency of symptoms, eliminate the symptoms and/orunderlying cause, prevent the occurrence of symptoms and/or theirunderlying cause, and/or improve or remediate the damage that resultsfrom or is associated with diabetes, obesity and dyslipidemia. In someembodiments, the effective amount is a therapeutically effective amountor a prophylactically effective amount. A “therapeutically effectiveamount” is an amount sufficient to remedy a disease state (e.g.,diabetes, obesity or dyslipidemia) or symptoms, particularly a state orsymptoms associated with the disease state, or otherwise prevent,hinder, retard or reverse the progression of the disease state or anyother undesirable symptom associated with the disease in any waywhatsoever. A “prophylactically effective amount” is an amount of apharmaceutical composition that, when administered to a subject, willhave the intended prophylactic effect, e.g., preventing or delaying theonset (or reoccurrence) of diabetes, obesity or dyslipidemia, orreducing the likelihood of the onset (or reoccurrence) of diabetes,obesity or dyslipidemia or associated symptoms. The full therapeutic orprophylactic effect does not necessarily occur by administration of onedose, and may occur only after administration of a series of doses.Thus, a therapeutically or prophylactically effective amount can beadministered in one or more administrations.

“Amino acid” takes its normal meaning in the art. The twentynaturally-occurring amino acids and their abbreviations followconventional usage. See, Immunology—A Synthesis, 2nd Edition, (E. S.Golub and D. R. Green, eds.), Sinauer Associates: Sunderland, Mass.(1991), incorporated herein by reference for any purpose. Stereoisomers(e.g., D-amino acids) of the twenty conventional amino acids, unnaturalor non-naturally occurring or encoded amino acids such asα-,α-disubstituted amino acids, N-alkyl amino acids, and otherunconventional amino acids can also be suitable components forpolypeptides and are included in the phrase “amino acid.” Examples ofnon-natural and non-naturally encoded amino acids (which can besubstituted for any naturally-occurring amino acid found in any sequencedisclosed herein, as desired) include: 4-hydroxyproline,γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine,O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine,5-hydroxylysine, σ-N-methylarginine, and other similar amino acids andimino acids (e.g., 4-hydroxyproline). In the polypeptide notation usedherein, the left-hand direction is the amino terminal direction and theright-hand direction is the carboxyl-terminal direction, in accordancewith standard usage and convention. A non-limiting lists of examples ofnon-naturally occurring/encoded amino acids that can be inserted into anantigen binding protein sequence or substituted for a wild-type residuein an antigen binding sequence include β-amino acids, homoamino acids,cyclic amino acids and amino acids with derivatized side chains.Examples include (in the L-form or D-form; abbreviated as inparentheses): citrulline (Cit), homocitrulline (hCit),Nα-methylcitrulline (NMeCit), Nα-methylhomocitrulline (Nα-MeHoCit),ornithine (Om), Nα-Methylomithine (Nα-MeOrn or NMeOrn), sarcosine (Sar),homolysine (hLys or hK), homoarginine (hArg or hR), homoglutamine (hQ),Nα-methylarginine (NMeR), Nα-methylleucine (Nα-MeL or NMeL),N-methylhomolysine (NMeHoK), Nα-methylglutamine (NMeQ), norleucine(Nle), norvaline (Nva), 1,2,3,4-tetrahydroisoquinoline (Tic),Octahydroindole-2-carboxylic acid (Oic), 3-(1-naphthy)alanine (1-Nal),3-(2-naphthyl)alanine (2-Nal), 1,2,3,4-tetrahydroisoquinoline (Tic),2-indanylglycine (IgI), para-iodophenylalanine (pI-Phe),para-aminophenylalanine (4AmP or 4-Amino-Phe), 4-guanidino phenylalanine(Guf), glycyllysine (abbreviated “K(Nε-glycyl)” or “K(glycyl)” or“K(gly)”), nitrophenylalanine (nitrophe), aminophenylalanine (aminopheor Amino-Phe), benzylphenylalanine (benzylphe), γ-carboxyglutamic acid(γ-carboxyglu), hydroxyproline (hydroxypro), p-carboxyl-phenylalanine(Cpa), α-aminoadipic acid (Aad), Nα-methyl valine (NMeVal), N-α-methylleucine (NMeLeu), Nα-methylnorleucine (NMeNle), cyclopentylglycine(Cpg), cyclohexylglycine (Chg), acetylarginine (acetylarg), α,β-diaminopropionoic acid (Dpr), α, γ-diaminobutyric acid (Dab),diaminopropionic acid (Dap), cyclohexylalanine (Cha),4-methyl-phenylalanine (MePhe), β, β-diphenyl-alanine (BiPhA),aminobutyric acid (Abu), 4-phenyl-phenylalanine (or biphenylalanine;4Bip), α-amino-isobutyric acid (Aib), beta-alanine, beta-aminopropionicacid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid,aminopimelic acid, desmosine, diaminopimelic acid, N-ethylglycine,N-ethylaspargine, hydroxylysine, allo-hydroxylysine, isodesmosine,allo-isoleucine, N-methylglycine, N-methylisoleucine, N-methylvaline,4-hydroxyproline (Hyp), γ-carboxyglutamate, ε-N,N,N-trimethyllysine,ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine,3-methylhistidine, 5-hydroxylysine, ω-methylarginine, 4-Amino-O-PhthalicAcid (4APA), and other similar amino acids, and derivatized forms of anyof those specifically listed.

II. General Overview

Antigen-binding proteins that bind to a complex comprising β-Klotho andat least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are providedherein. A unique property of the antigen binding proteins disclosedherein is the agonistic nature of these proteins, specifically theability to mimic the in vivo effect of FGF21 and to induce FGF21-likesignaling. More remarkably and specifically, some of the antigen bindingproteins disclosed herein induce FGF21-like signaling in several invitro cell-based assay, including the ELK-luciferase reporter assay ofExample 4 under the following conditions: (1) the binding to andactivity of the FGF21 receptor is β-Klotho dependent; (2) the activityis selective to the FGFR/β-Klotho complex; (3) the binding to theFGFR1c/βKlotho complex triggers FGF21-like signaling pathways; and (4)the potency (EC50) is comparable to a wild-type FGF21 standardcomprising the mature form of SEQ ID NO: 2, as measured in the followingcell-based assays: (1) the recombinant FGF21 receptor mediatedluciferase-reporter cell assay of Example 4; (2) the ERK-phosphorylationin the recombinant FGF21 receptor mediated cell assay of Example 4; and(3) ERK-phosphorylation in human adipocytes as described in more detailsin Example 6. The disclosed antigen binding proteins, therefore, areexpected to exhibit activities in vivo that are consistent with thenatural biological function of FGF21. This property makes the disclosedantigen binding proteins viable therapeutics for the treatment ofmetabolic diseases such as type 2 diabetes, obesity, dyslipidemia, NASH,cardiovascular disease, metabolic syndrome and broadly any disease orcondition in which it is desirable to mimic or augment the in vivoeffects of FGF21.

In some embodiments of the present disclosure the antigen bindingproteins provided can comprise polypeptides into which one or morecomplementary determining regions (CDRs) can be embedded and/or joined.In such antigen binding proteins, the CDRs can be embedded into a“framework” region, which orients the CDR(s) such that the properantigen binding properties of the CDR(s) is achieved. In general, suchantigen binding proteins that are provided can facilitate or enhance theinteraction between an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c) andβ-Klotho, and can substantially induce FGF21-like signaling.Accordingly, the antigen binding proteins provided herein mimic the invivo role of FGF21 and are thus “agonistic” and offer potentialtherapeutic benefit for the range of conditions which benefit from FGF21therapy, including type 2 diabetes, obesity, dyslipidemia, NASH,cardiovascular disease, metabolic syndrome and broadly any disease orcondition in which it is desirable to mimic or augment the in vivoeffects of FGF21.

Certain antigen binding proteins described herein are antibodies or arederived from antibodies. In certain embodiments, the polypeptidestructure of the antigen binding proteins is based on antibodies,including, but not limited to, monoclonal antibodies, bispecificantibodies, minibodies, domain antibodies, synthetic antibodies(sometimes referred to herein as “antibody mimetics”), chimericantibodies, humanized antibodies, human antibodies, antibody fusions(sometimes referred to herein as “antibody conjugates”), hemibodies andfragments thereof. The various structures are further described hereinbelow.

The antigen binding proteins provided herein have been demonstrated tobind to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c, and particularly to a complex comprisinghuman β-Klotho and a human FGFR (e.g., a human FGFR1c, a human FGFR2c ora human FGFR3c). As described and shown in the Examples presentedherein, based Western blot results, known commercially-availableanti-β-Klotho or anti-FGFR1c antibodies bind to denatured β-Klotho orFGFR1c whereas the antigen binding protein (which are agonisticantibodies) do not. Conversely, the provided antigen binding proteinsrecognize the native structure of the FGFR1c and β-Klotho on the cellsurface whereas the commercial antibodies do not. The antigen bindingproteins that are provided therefore mimic the natural in vivobiological activity of FGF21. As a consequence, the antigen bindingproteins provided herein are capable of activating FGF21-like signalingactivity. In particular, the disclosed antigen binding proteins can haveone or more of the following activities in vivo: induction of FGF21-likesignal transduction pathways, lowering blood glucose levels, loweringcirculating lipid levels, improving metabolic parameters and otherphysiological effects induced in vivo by the formation of the ternarycomplex of an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c), β-Klotho and FGF21,for example conditions such as type 2 diabetes, obesity, dyslipidemia,NASH, cardiovascular disease, and metabolic syndrome.

The antigen binding proteins that specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c that are disclosed herein have a variety of utilities. Someof the antigen binding proteins, for instance, are useful in specificbinding assays, in the affinity purification of a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c,including the human forms of these disclosed proteins, and in screeningassays to identify other agonists of FGF21-like signaling activity.

The antigen binding proteins that specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c that are disclosed herein can be used in a variety oftreatment applications, as explained herein. For example, certainantigen binding proteins are useful for treating conditions associatedwith FGF21-like signaling processes in a patient, such as reducing,alleviating, or treating type 2 diabetes, obesity, dyslipidemia, NASH,cardiovascular disease, and metabolic syndrome. Other uses for theantigen binding proteins include, for example, diagnosis of diseases orconditions associated with β-Klotho, FGFR1c, FGFR2c, FGFR3c, FGFR4 orFGF21, and screening assays to determine the presence or absence ofthese molecules. Some of the antigen binding proteins described hereincan be useful in treating conditions, symptoms and/or the pathologyassociated with decreased FGF21-like signaling activity. Exemplaryconditions include, but are not limited to, diabetes, obesity, NASH anddyslipidemia.

FGF21

The antigen binding proteins disclosed herein induce FGF21-mediatedsignaling, as defined herein. In vivo, the mature form of FGF21 is theactive form of the molecule. The nucleotide sequence encoding fulllength FGF21 is provided; the nucleotides encoding the signal sequenceare underlined.

(SEQ ID NO: 1) ATG GAC TCG GAC GAG ACC GGG TTC GAG CAC TCA GGACTG TGG GTT TCT GTG CTG GCT GGT CTT CTG CTG GGA GCC TGC CAG GCA CAC CCCATC CCT GAC TCC AGT CCT CTC CTG CAA TTC GGG GGC CAA GTC CGG CAG CGG TACCTC TAC ACA GAT GAT GCC CAG CAG ACA GAA GCC CAC CTG GAG ATC AGG GAG GATGGG ACG GTG GGG GGC GCT GCT GAC CAG AGC CCC GAA AGT CTC CTG CAG CTG AAAGCC TTG AAG CCG GGA GTT ATT CAA ATC TTG GGA GTC AAG ACA TCC AGG TTC CTGTGC CAG CGG CCA GAT GGG GCC CTG TAT GGA TCG CTC CAC TTT GAC CCT GAG GCCTGC AGC TTC CGG GAG CTG CTT CTT GAG GAC GGA TAC AAT GTT TAC CAG TCC GAAGCC CAC GGC CTC CCG CTG CAC CTG CCA GGG AAC AAG TCC CCA CAC CGG GAC CCTGCA CCC CGA GGA CCA GCT CGC TTC CTG CCA CTA CCA GGC CTG CCC CCC GCA CCCCCG GAG CCA CCC GGA ATC CTG GCC CCC CAG CCC CCC GAT GTG GGC TCC TCG GACCCT CTG AGC ATG GTG GGA CCT TCC CAG GGC CGA AGC CCC AGC TAC GCT TCC TGA

The amino acid sequence of full length FGF21 is provided; the aminoacids that make up the signal sequence are underlined:

(SEQ ID NO: 2) M D S D E T G F E H S G L W V S V L A G L L L G A C Q A HP I P D S S P L L Q F G G Q V R Q R Y L Y T D D A Q Q T E A H L E I R ED G T V G G A A D Q S P E S L L Q L K A L K P G V I Q I L G V K T S R FL C Q R P D G A L Y G S L H F D P E A C S F R E L L L E D G Y N V Y Q SE A H G L P L H L P G N K S P H R D P A P R G P A R F L P L P G L P P AP P E P P G I L A P Q P P D V G S S D P L S M V G P S Q G R S P S Y A S

FGFR1c

The antigen binding proteins disclosed herein bind to FGFR1c, inparticular human FGFR1c, when associated with β-Klotho. The nucleotidesequence encoding human FGFR1c (GenBank Accession Number NM_023110) isprovided:

(SEQ ID NO: 3) ATGTGGAGCTGGAAGTGCCTCCTCTTCTGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCCGTCCCCGACCTTGCCTGAACAAGCCCAGCCCTGGGGAGCCCCTGTGGAAGTGGAGTCCTTCCTGGTCCACCCCGGTGACCTGCTGCAGCTTCGCTGTCGGCTGCGGGACGATGTGCAGAGCATCAACTGGCTGCGGGACGGGGTGCAGCTGGCGGAAAGCAACCGCACCCGCATCACAGGGGAGGAGGTGGAGGTGCAGGACTCCGTGCCCGCAGACTCCGGCCTCTATGCTTGCGTAACCAGCAGCCCCTCGGGCAGTGACACCACCTACTTCTCCGTCAATGTTTCAGATGCTCTCCCCTCCTCGGAGGATGATGATGATGATGATGACTCCTCTTCAGAGGAGAAAGAAACAGATAACACCAAACCAAACCGTATGCCCGTAGCTCCATATTGGACATCACCAGAAAAGATGGAAAAGAAATTGCATGCAGTGCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACACCAAACCCAACACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAACCTGACCACAGAATTGGAGGCTACAAGGTCCGTTATGCCACCTGGAGCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACTACACCTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCAGCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGCCAACAAAACAGTGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGACCCGCAGCCGCACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACAACCTGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGACAAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACGTGCTTGGCGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAAGCCCTGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTATTGCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGATGAAGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGGCCAAGAGCATCCCTCTGCGCAGACAGGTAACAGTGTCTGCTGACTCCAGTGCATCCATGAACTCTGGGGTTCTTCTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCATGCTAGCAGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTCGGGACAGACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAGGACAAACCCAACCGTGTGACCAAAGTGGCTGTGAAGATGTTGAAGTCGGACGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAATGGAGATGATGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCTGGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATCGTGGAGTATGCCTCCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCCCCAGGGCTGGAATACTGCTACAACCCCAGCCACAACCCAGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGGCCCGAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACCTGGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTTGGCCTCGCACGGGACATTCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGAAGTGGATGGCACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGATGTGTGGTCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCCGGTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGCCCAGTAACTGCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGCCCTCACAGAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTTGACCTCCAACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCAGCTTTCCCGACACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTCATGAGCCGCTGCCCGAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATGGCGGACTCAAACGCCGC TGA.

The amino acid sequence of human FGFR1c (GenBank Accession NumberNP_075598) is provided:

(SEQ ID NO: 4) MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKSIPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLP RHPAQLANGGLKRR.

The antigen binding proteins described herein bind the extracellularportion of FGFR1c. An example of an extracellular region of FGFR1c is:

(SEQ ID NO: 5) MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLY.

As described herein, FGFR1c proteins can also include fragments. As usedherein, the terms are used interchangeably to mean a receptor, inparticular and unless otherwise specified, a human receptor, that uponassociation with β-Klotho and FGF21 induces FGF21-like signalingactivity.

The term FGFR1c also includes post-translational modifications of theFGFR1c amino acid sequence, for example, possible N-linked glycosylationsites. Thus, the antigen binding proteins can bind to or be generatedfrom proteins glycosylated at one or more of the positions.

β-Klotho

The antigen binding proteins disclosed herein bind to β-Klotho, inparticular human β-Klotho. The nucleotide sequence encoding humanβ-Klotho (GenBank Accession Number NM_175737) is provided:

(SEQ ID NO: 6) ATGAAGCCAGGCTGTGCGGCAGGATCTCCAGGGAATGAATGGATTTTCTTCAGCACTGATGAAATAACCACACGCTATAGGAATACAATGTCCAACGGGGGATTGCAAAGATCTGTCATCCTGTCAGCACTTATTCTGCTACGAGCTGTTACTGGATTCTCTGGAGATGGAAGAGCTATATGGTCTAAAAATCCTAATTTTACTCCGGTAAATGAAAGTCAGCTGTTTCTCTATGACACTTTCCCTAAAAACTTTTTCTGGGGTATTGGGACTGGAGCATTGCAAGTGGAAGGGAGTTGGAAGAAGGATGGAAAAGGACCTTCTATATGGGATCATTTCATCCACACACACCTTAAAAATGTCAGCAGCACGAATGGTTCCAGTGACAGTTATATTTTTCTGGAAAAAGACTTATCAGCCCTGGATTTTATAGGAGTTTCTTTTTATCAATTTTCAATTTCCTGGCCAAGGCTTTTCCCCGATGGAATAGTAACAGTTGCCAACGCAAAAGGTCTGCAGTACTACAGTACTCTTCTGGACGCTCTAGTGCTTAGAAACATTGAACCTATAGTTACTTTATACCACTGGGATTTGCCTTTGGCACTACAAGAAAAATATGGGGGGTGGAAAAATGATACCATAATAGATATCTTCAATGACTATGCCACATACTGTTTCCAGATGTTTGGGGACCGTGTCAAATATTGGATTACAATTCACAACCCATATCTAGTGGCTTGGCATGGGTATGGGACAGGTATGCATGCCCCTGGAGAGAAGGGAAATTTAGCAGCTGTCTACACTGTGGGACACAACTTGATCAAGGCTCACTCGAAAGTTTGGCATAACTACAACACACATTTCCGCCCACATCAGAAGGGTTGGTTATCGATCACGTTGGGATCTCATTGGATCGAGCCAAACCGGTCGGAAAACACGATGGATATATTCAAATGTCAACAATCCATGGTTTCTGTGCTTGGATGGTTTGCCAACCCTATCCATGGGGATGGCGACTATCCAGAGGGGATGAGAAAGAAGTTGTTCTCCGTTCTACCCATTTTCTCTGAAGCAGAGAAGCATGAGATGAGAGGCACAGCTGATTTCTTTGCCTTTTCTTTTGGACCCAACAACTTCAAGCCCCTAAACACCATGGCTAAAATGGGACAAAATGTTTCACTTAATTTAAGAGAAGCGCTGAACTGGATTAAACTGGAATACAACAACCCTCGAATCTTGATTGCTGAGAATGGCTGGTTCACAGACAGTCGTGTGAAAACAGAAGACACCACGGCCATCTACATGATGAAGAATTTCCTCAGCCAGGTGCTTCAAGCAATAAGGTTAGATGAAATACGAGTGTTTGGTTATACTGCCTGGTCTCTCCTGGATGGCTTTGAATGGCAGGATGCTTACACCATCCGCCGAGGATTATTTTATGTGGATTTTAACAGTAAACAGAAAGAGCGGAAACCTAAGTCTTCAGCACACTACTACAAACAGATCATACGAGAAAATGGTTTTTCTTTAAAAGAGTCCACGCCAGATGTGCAGGGCCAGTTTCCCTGTGACTTCTCCTGGGGTGTCACTGAATCTGTTCTTAAGCCCGAGTCTGTGGCTTCGTCCCCACAGTTCAGCGATCCTCATCTGTACGTGTGGAACGCCACTGGCAACAGACTGTTGCACCGAGTGGAAGGGGTGAGGCTGAAAACACGACCCGCTCAATGCACAGATTTTGTAAACATCAAAAAACAACTTGAGATGTTGGCAAGAATGAAAGTCACCCACTACCGGTTTGCTCTGGATTGGGCCTCGGTCCTTCCCACTGGCAACCTGTCCGCGGTGAACCGACAGGCCCTGAGGTACTACAGGTGCGTGGTCAGTGAGGGGCTGAAGCTTGGCATCTCCGCGATGGTCACCCTGTATTATCCGACCCACGCCCACCTAGGCCTCCCCGAGCCTCTGTTGCATGCCGACGGGTGGCTGAACCCATCGACGGCCGAGGCCTTCCAGGCCTACGCTGGGCTGTGCTTCCAGGAGCTGGGGGACCTGGTGAAGCTCTGGATCACCATCAACGAGCCTAACCGGCTAAGTGACATCTACAACCGCTCTGGCAACGACACCTACGGGGCGGCGCACAACCTGCTGGTGGCCCACGCCCTGGCCTGGCGCCTCTACGACCGGCAGTTCAGGCCCTCACAGCGCGGGGCCGTGTCGCTGTCGCTGCACGCGGACTGGGCGGAACCCGCCAACCCCTATGCTGACTCGCACTGGAGGGCGGCCGAGCGCTTCCTGCAGTTCGAGATCGCCTGGTTCGCCGAGCCGCTCTTCAAGACCGGGGACTACCCCGCGGCCATGAGGGAATACATTGCCTCCAAGCACCGACGGGGGCTTTCCAGCTCGGCCCTGCCGCGCCTCACCGAGGCCGAAAGGAGGCTGCTCAAGGGCACGGTCGACTTCTGCGCGCTCAACCACTTCACCACTAGGTTCGTGATGCACGAGCAGCTGGCCGGCAGCCGCTACGACTCGGACAGGGACATCCAGTTTCTGCAGGACATCACCCGCCTGAGCTCCCCCACGCGCCTGGCTGTGATTCCCTGGGGGGTGCGCAAGCTGCTGCGGTGGGTCCGGAGGAACTACGGCGACATGGACATTTACATCACCGCCAGTGGCATCGACGACCAGGCTCTGGAGGATGACCGGCTCCGGAAGTACTACCTAGGGAAGTACCTTCAGGAGGTGCTGAAAGCATACCTGATTGATAAAGTCAGAATCAAAGGCTATTATGCATTCAAACTGGCTGAAGAGAAATCTAAACCCAGATTTGGATTCTTCACATCTGATTTTAAAGCTAAATCCTCAATACAATTTTACAACAAAGTGATCAGCAGCAGGGGCTTCCCTTTTGAGAACAGTAGTTCTAGATGCAGTCAGACCCAAGAAAATACAGAGTGCACTGTCTGCTTATTCCTTGTGCAGAAGAAACCACTGATATTCCTGGGTTGTTGCTTCTTCTCCACCCTGGTTCTACTCTTATCAATTGCCATTTTTCAAAGGCAGAAGAGAAGAAAGTTTTGGAAAGCAAAAAACTTACAACACATACCATTAAAGAAAGGCAAGA GAGTTGTTAGCTAA.

The amino acid sequence of full length human β-Klotho (GenBank AccessionNumber NP_783864) is provided:

(SEQ ID NO: 7) MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDRQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS.

The antigen binding proteins described herein bind the extracellularportion of β-Klotho. An example of an extracellular region of β-Klothois:

(SEQ ID NO: 8) MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDRQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKP.

The murine form of β-Klotho, and fragments and subsequences thereof, canbe of use in studying and/or constructing the molecules provided herein.The nucleotide sequence encoding murine β-Klotho (GenBank AccessionNumber NM_031180) is provided:

(SEQ ID NO: 9) ATGAAGACAGGCTGTGCAGCAGGGTCTCCGGGGAATGAATGGATTTTCTTCAGCTCTGATGAAAGAAACACACGCTCTAGGAAAACAATGTCCAACAGGGCACTGCAAAGATCTGCCGTGCTGTCTGCGTTTGTTCTGCTGCGAGCTGTTACCGGCTTCTCCGGAGACGGGAAAGCAATATGGGATAAAAAACAGTACGTGAGTCCGGTAAACCCAAGTCAGCTGTTCCTCTATGACACTTTCCCTAAAAACTTTTCCTGGGGCGTTGGGACCGGAGCATTTCAAGTGGAAGGGAGTTGGAAGACAGATGGAAGAGGACCCTCGATCTGGGATCGGTACGTCTACTCACACCTGAGAGGTGTCAACGGCACAGACAGATCCACTGACAGTTACATCTTTCTGGAAAAAGACTTGTTGGCTCTGGATTTTTTAGGAGTTTCTTTTTATCAGTTCTCAATCTCCTGGCCACGGTTGTTTCCCAATGGAACAGTAGCAGCAGTGAATGCGCAAGGTCTCCGGTACTACCGTGCACTTCTGGACTCGCTGGTACTTAGGAATATCGAGCCCATTGTTACCTTGTACCATTGGGATTTGCCTCTGACGCTCCAGGAAGAATATGGGGGCTGGAAAAATGCAACTATGATAGATCTCTTCAACGACTATGCCACATACTGCTTCCAGACCTTTGGAGACCGTGTCAAATATTGGATTACAATTCACAACCCTTACCTTGTTGCTTGGCATGGGTTTGGCACAGGTATGCATGCACCAGGAGAGAAGGGAAATTTAACAGCTGTCTACACTGTGGGACACAACCTGATCAAGGCACATTCGAAAGTGTGGCATAACTACGACAAAAACTTCCGCCCTCATCAGAAGGGTTGGCTCTCCATCACCTTGGGGTCCCATTGGATAGAGCCAAACAGAACAGACAACATGGAGGACGTGATCAACTGCCAGCACTCCATGTCCTCTGTGCTTGGATGGTTCGCCAACCCCATCCACGGGGACGGCGACTACCCTGAGTTCATGAAGACGGGCGCCATGATCCCCGAGTTCTCTGAGGCAGAGAAGGAGGAGGTGAGGGGCACGGCTGATTTCTTTGCCTTTTCCTTCGGGCCCAACAACTTCAGGCCCTCAAACACCGTGGTGAAAATGGGACAAAATGTATCACTCAACTTAAGGCAGGTGCTGAACTGGATTAAACTGGAATACGATGACCCTCAAATCTTGATTTCGGAGAACGGCTGGTTCACAGATAGCTATATAAAGACAGAGGACACCACGGCCATCTACATGATGAAGAATTTCCTAAACCAGGTTCTTCAAGCAATAAAATTTGATGAAATCCGCGTGTTTGGTTATACGGCCTGGACTCTCCTGGATGGCTTTGAGTGGCAGGATGCCTATACGACCCGACGAGGGCTGTTTTATGTGGACTTTAACAGTGAGCAGAAAGAGAGGAAACCCAAGTCCTCGGCTCATTACTACAAGCAGATCATACAAGACAACGGCTTCCCTTTGAAAGAGTCCACGCCAGACATGAAGGGTCGGTTCCCCTGTGATTTCTCTTGGGGAGTCACTGAGTCTGTTCTTAAGCCCGAGTTTACGGTCTCCTCCCCGCAGTTTACCGATCCTCACCTGTATGTGTGGAATGTCACTGGCAACAGATTGCTCTACCGAGTGGAAGGGGTAAGGCTGAAAACAAGACCATCCCAGTGCACAGATTATGTGAGCATCAAAAAACGAGTTGAAATGTTGGCAAAAATGAAAGTCACCCACTACCAGTTTGCTCTGGACTGGACCTCTATCCTTCCCACTGGCAATCTGTCCAAAGTTAACAGACAAGTGTTAAGGTACTATAGGTGTGTGGTGAGCGAAGGACTGAAGCTGGGCGTCTTCCCCATGGTGACGTTGTACCACCCAACCCACTCCCATCTCGGCCTCCCCCTGCCACTTCTGAGCAGTGGGGGGTGGCTAAACATGAACACAGCCAAGGCCTTCCAGGACTACGCTGAGCTGTGCTTCCGGGAGTTGGGGGACTTGGTGAAGCTCTGGATCACCATCAATGAGCCTAACAGGCTGAGTGACATGTACAACCGCACGAGTAATGACACCTACCGTGCAGCCCACAACCTGATGATCGCCCATGCCCAGGTCTGGCACCTCTATGATAGGCAGTATAGGCCGGTCCAGCATGGGGCTGTGTCGCTGTCCTTACATTGCGACTGGGCAGAACCTGCCAACCCCTTTGTGGATTCACACTGGAAGGCAGCCGAGCGCTTCCTCCAGTTTGAGATCGCCTGGTTTGCAGATCCGCTCTTCAAGACTGGCGACTATCCATCGGTTATGAAGGAATACATCGCCTCCAAGAACCAGCGAGGGCTGTCTAGCTCAGTCCTGCCGCGCTTCACCGCGAAGGAGAGCAGGCTGGTGAAGGGTACCGTCGACTTCTACGCACTGAACCACTTCACTACGAGGTTCGTGATACACAAGCAGCTGAACACCAACCGCTCAGTTGCAGACAGGGACGTCCAGTTCCTGCAGGACATCACCCGCCTAAGCTCGCCCAGCCGCCTGGCTGTAACACCCTGGGGAGTGCGCAAGCTCCTTGCGTGGATCCGGAGGAACTACAGAGACAGGGATATCTACATCACAGCCAATGGCATCGATGACCTGGCTCTAGAGGATGATCAGATCCGAAAGTACTACTTGGAGAAGTATGTCCAGGAGGCTCTGAAAGCATATCTCATTGACAAGGTCAAAATCAAAGGCTACTATGCATTCAAACTGACTGAAGAGAAATCTAAGCCTAGATTTGGATTTTTCACCTCTGACTTCAGAGCTAAGTCCTCTGTCCAGTTTTACAGCAAGCTGATCAGCAGCAGTGGCCTCCCCGCTGAGAACAGAAGTCCTGCGTGTGGTCAGCCTGCGGAAGACACAGACTGCACCATTTGCTCATTTCTCGTGGAGAAGAAACCACTCATCTTCTTCGGTTGCTGCTTCATCTCCACTCTGGCTGTACTGCTATCCATCACCGTTTTTCATCATCAAAAGAGAAGAAAATTCCAGAAAGCAAGGAACTTACAAAATATACCATTGAAGAAAGGCCACAGCAGAGT TTTCAGCTAA.

The amino acid sequence of full length murine β-Klotho (GenBankAccession Number NP_112457) is provided:

(SEQ ID NO: 10) MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAVTGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQFYSKLISSSGLPAENRSPACGQPAEDTDCTICSFLVEKKPLIFFGCCFISTLAVLLSITVFHHQKRRKFQKARNLQNIPLKKGHSRVFS.

As described herein, β-Klotho proteins can also include fragments. Asused herein, the terms are used interchangeably to mean a co-receptor,in particular and unless otherwise specified, a human co-receptor, thatupon association with FGFR1c and FGF21 induces FGF21-like signalingactivity.

The term β-Klotho also includes post-translational modifications of theβ-Klotho amino acid sequence, for example, possible N-linkedglycosylation sites. Thus, the antigen binding proteins can bind to orbe generated from proteins glycosylated at one or more of the positions.

Antigen Binding Proteins that Specifically Bind to a Complex Comprisingβ-Klotho and an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c)

A variety of selective binding agents useful for modulating FGF21-likesignaling are provided. These agents include, for instance, antigenbinding proteins that contain an antigen binding domain (e.g., singlechain antibodies, domain antibodies, hemibodies, immunoadhesions, andpolypeptides with an antigen binding region) and specifically bind to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c, in particular a complex comprising human β-Klotho anda human FGFR (e.g., human FGFR1c, human FGFR2c or human FGFR3c). Some ofthe agents, for example, are useful in mimicking the signaling effectgenerated in vivo by the association of an FGFR (e.g., FGFR1c, FGFR2c orFGFR3c) with β-Klotho and with FGF21, and can thus be used to enhance ormodulate one or more activities associated with FGF21-like signaling.

In general, the antigen binding proteins that are provided typicallycomprise one or more CDRs as described herein (e.g., 1, 2, 3, 4, 5 or 6CDRs). In some embodiments the antigen binding proteins are naturallyexpressed by clones, while in other embodiments, the antigen bindingprotein can comprise (a) a polypeptide framework structure and (b) oneor more CDRs that are inserted into and/or joined to the polypeptideframework structure. In some of these embodiments a CDR forms acomponent of a heavy or light chains expressed by the clones describedherein; in other embodiments a CDR can be inserted into a framework inwhich the CDR is not naturally expressed. A polypeptide frameworkstructure can take a variety of different forms. For example, apolypeptide framework structure can be, or comprise, the framework of anaturally occurring antibody, or fragment or variant thereof, or it canbe completely synthetic in nature. Examples of various antigen bindingprotein structures are further described below.

In some embodiments in which the antigen binding protein comprises (a) apolypeptide framework structure and (b) one or more CDRs that areinserted into and/or joined to the polypeptide framework structure, thepolypeptide framework structure of an antigen binding protein is anantibody or is derived from an antibody, including, but not limited to,monoclonal antibodies, bispecific antibodies, minibodies, domainantibodies, synthetic antibodies (sometimes referred to herein as“antibody mimetics”), chimeric antibodies, humanized antibodies,antibody fusions (sometimes referred to as “antibody conjugates”), andportions or fragments of each, respectively. In some instances, theantigen binding protein is an immunological fragment of an antibody(e.g., a Fab, a Fab′, a F(ab′)₂, or a scFv).

Certain of the antigen binding proteins as provided herein specificallybind to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c, including the human forms of theseproteins. In one embodiment, an antigen binding protein specificallybinds to both human FGFR1c comprising the amino acid sequence of SEQ IDNO: 4, and human β-Klotho comprising the amino acid sequence of SEQ IDNO: 7, and in another embodiment an antigen binding protein specificallybinds to both human FGFR1c comprising the amino acid sequence of SEQ IDNO: 4 and human β-Klotho having the amino acid sequence of SEQ ID NO: 7and induces FGF21-like signaling. Thus, an antigen binding protein can,but need not, induce FGF21-like signaling.

Antigen Binding Protein Structure

Some of the antigen binding proteins that specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c, including the human forms of these proteins, providedherein have a structure typically associated with naturally occurringantibodies. The structural units of these antibodies typically compriseone or more tetramers, each composed of two identical couplets ofpolypeptide chains, though some species of mammals also produceantibodies having only a single heavy chain. In a typical antibody, eachpair or couplet includes one full-length “light” chain (in certainembodiments, about 25 kDa) and one full-length “heavy” chain (in certainembodiments, about 50-70 kDa). Each individual immunoglobulin chain iscomposed of several “immunoglobulin domains,” each consisting of roughly90 to 110 amino acids and expressing a characteristic folding pattern.These domains are the basic units of which antibody polypeptides arecomposed. The amino-terminal portion of each chain typically includes avariable domain that is responsible for antigen recognition. Thecarboxy-terminal portion is more conserved evolutionarily than the otherend of the chain and is referred to as the “constant region” or “Cregion”. Human light chains generally are classified as kappa (“κ”) andlambda (“λ”) light chains, and each of these contains one variabledomain and one constant domain. Heavy chains are typically classified asmu, delta, gamma, alpha, or epsilon chains, and these define theantibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. IgG hasseveral subtypes, including, but not limited to, IgG1, IgG2, IgG3, andIgG4. IgM subtypes include IgM, and IgM2. IgA subtypes include IgA1 andIgA2. In humans, the IgA and IgD isotypes contain four heavy chains andfour light chains; the IgG and IgE isotypes contain two heavy chains andtwo light chains; and the IgM isotype contains five heavy chains andfive light chains. The heavy chain C region typically comprises one ormore domains that can be responsible for effector function. The numberof heavy chain constant region domains will depend on the isotype. IgGheavy chains, for example, each contain three C region domains known asC_(H)1, C_(H)2 and C_(H)3. The antibodies that are provided can have anyof these isotypes and subtypes. In certain embodiments, an antigenbinding protein that specifically binds to a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c is anantibody of the IgG1, IgG2, or IgG4 subtype.

In full-length light and heavy chains, the variable and constant regionsare joined by a “J” region of about twelve or more amino acids, with theheavy chain also including a “D” region of about ten more amino acids.See, e.g., Fundamental Immunology, 2nd ed., Ch. 7 (Paul, W., ed.) 1989,New York: Raven Press (hereby incorporated by reference in its entiretyfor all purposes). The variable regions of each light/heavy chain pairtypically form the antigen binding site.

One example of an IgG2 heavy constant domain of an exemplary monoclonalantibody that specifically binds to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has the amino acidsequence:

(SEQ ID NO: 11) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.

One example of a kappa light constant domain of an exemplary monoclonalantibody that binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has the amino acid sequence:

(SEQ ID NO: 12) TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP VTKSFNRGEC.

One example of a lambda light constant domain of an exemplary monoclonalantibody that binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has the amino acid sequence:

(SEQ ID NO: 13) QPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA PTECS.

Variable regions of immunoglobulin chains generally exhibit the sameoverall structure, comprising relatively conserved framework regions(FR) joined by three hypervariable regions, more often called“complementarity determining regions” or CDRs. The CDRs from the twochains of each heavy chain/light chain pair mentioned above typicallyare aligned by the framework regions to form a structure that bindsspecifically with a specific epitope on the target protein (e.g., acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c. From N-terminal to C-terminal, naturally-occurringlight and heavy chain variable regions both typically conform with thefollowing order of these elements: FR1, CDR1, FR2, CDR2, FR3, CDR3 andFR4. A numbering system has been devised for assigning numbers to aminoacids that occupy positions in each of these domains. This numberingsystem is defined in Kabat et al., (1991) “Sequences of Proteins ofImmunological Interest”, 5th Ed., US Dept. of Health and Human Services,PHS, NIH, NIH Publication no. 91-3242. Although presented using theKabat nomenclature system, as desired, the CDRs disclosed herein canalso be redefined according an alternative nomenclature scheme, such asthat of Chothia (see Chothia & Lesk, (1987) J. Mol. Biol. 196:901-917;Chothia et al., (1989) Nature 342:878-883 or Honegger & Pluckthun,(2001) J. Mol. Biol. 309:657-670).

The various heavy chain and light chain variable regions of antigenbinding proteins provided herein are depicted in Table 2. Each of thesevariable regions can be attached to the disclosed heavy and light chainconstant regions to form a complete antibody heavy and light chain,respectively. Further, each of the so-generated heavy and light chainsequences can be combined to form a complete antibody structure. Itshould be understood that the heavy chain and light chain variableregions provided herein can also be attached to other constant domainshaving different sequences than the exemplary sequences listed above.

Specific examples of some of the full length light and heavy chains ofthe antibodies that are provided and their corresponding amino acidsequences are summarized in Tables 1A and 1B. Table 1A shows exemplarylight chain sequences, and Table 1B shows exemplary heavy chainsequences.

TABLE 1A Exemplary Antibody Light Chain Sequences Contained SEQ ID inClone Designation NO: Amino Acid Sequence 63E6 L6 14DIQMTQSPSSLSASVGDRVTITCRTSQSISSYL NWYQQKPGKAPNLLIYAASSLQSGVPSRFSGSGSGTDFTLTISGLQPEDFSTYYCQQSYSTSL TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 66F7 L7 15 DIQMTQSPSSLSASVGDRVTITCRTSQSISNYLNVVYQQKPGKAPNLLIYAASSLQSGVPSRFS GSGSGTDFTLTISGLQPEDFSTYYCQQSYSTSLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 66D4 L18 16DIQMTQSPSSLSASVGDRITITCRASQIISRYL NWYQQNPGKAPKLLISAASSLQSGVPSRFSGSGSGPDFTLTISSLQPEDFTTYYCQQSYSSPLT FGGGTKVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 66B4 L11 17 DIQMTQSPSSVSSSVGDRVTITCRASQGISRWLAWYQQKPGKAPKLLIYAASSLKSGVPSRFS GSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 65B1 L19 18DIQMTQSPSSLSASVGDRVTITCRASQNINNY LNWYRQKPGKAPELLIYTTSSLQSGVPSRFSGSGSGTDFTLTISSLETEDFETYYCQQSYSTP LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 65B4 L21 19 SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVQWYQQKPGQAPVLVVYDDSDRPSGIPERFS GSNSGNTASLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTKLTVLGQPKANPTVTLFPPS SEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTP EQWKSHRSYSCQVTHEGSTVEKTVAPTECS 67A4 L2020 SYVLTQPPSVSVAPGQTARITCGGNNIGSKSV HWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDS SSDHVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 63A10v1 L22 21SYELTQPHSVSVATAQMARITCGGNNIGSKA VHWYQQKPGQDPVLVIYCDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWD SSSDGVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 63A10v2 L101 1835SYELTQPHSVSVATAQMARITCGGNNIGSKA VHWYQQKPGQDPVLVIYCDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQAWD STTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADG SPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 63A10v3 L102 1836SYELTQPPSVSVSPGQTANITCSGDKLGNRY TCWYQQKSGQSPVLVIYQDSERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAW DSTTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 65H11v1 L23 22SYELTQPHSVSVATAQMARITCGGNNIGSKT VHWFQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSS CDGVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 65H11v2 L103 1837SYELTQPPSVSVSPGQTANITCSGDKLGDRY VCWYQQKPGQSPVLVIYQDSKRPSGIPEQFSGSNSGNTATLTISGTQAIDEADYYCQAWDSI TVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSP VKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 67G10v1 L9 23SYELTQPHSVSVATAQMARITCGGNNIGSKA VHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSS SDGVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 67G10v2 L10 24SYELTQPPSVSVSPGQTASITCSGDKLGDKY ACWYQQKPGQSPVLVIYQDNERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDS TTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 64C8 L24 25DVVMTQSPLSLPVTLGQPASISRRSSPSLVYS DGNTYLNCFQQRPGHSPRRLIYKGSNWDSGVPDRFSGSGSGTDFTLKISRVEAEDVGIYYCI QDTHWPTCSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC 64A8 L1 26DIQMTQSPSSLSASVGDRVTITCRASQDIRND 67B4 LGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTEFTLTISTLQPEDFATYSCLQHNSY PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 63G8v1 L104 1838DIQMTQSPSSLSASVGDRVTITCRASQDIRND LGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTEFTLTISTLQPDDFATYSCLQHNSY PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 63G8v2 L105 1839DIQMTQSPSSLSASVGDRVTITCRASQGIRSG LGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTEFTLTVSSLQPEDFATYSCLQHNSY PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 63G8v3 L106 1840DIQMTQSPSSLSASVGDRVTITCRASQGIRSG LGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTEFTLTVSSLQPEDFATYSCLQHNTY PLTFGGGTKGEIRRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 66G2 L12 27 DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFS GSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 68D3v1 L2 28DIQMTQSPSSLSASVGDRVTITCRASQDIRND 68D3v2 LGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTEFTLTISTLQPDDFATYSCLQHNSY PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 65D1 L27 29 SYDLTQPPSVSVSPGQTASITCSGDKLGDKYVCWYQQKPGQSPVLVIYQDSKRPSGIPERFS GSNSGNTATLTISGIQAMDEADYYCQAWDSRVFGGGTKLTVLGQPKANPTVTLFPPSSEEL QANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQW KSHRSYSCQVTHEGSTVEKTVAPTECS 64H5 L8 30SYEMTQPLSVSVALGQTARITCGGNNIGSKN 65G4 VHWYQQKPGQAPVLVIYRDSKRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDS SSVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSP VKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 65D4 L26 31 SYELTQPLSVSVALGQTARIPCGGNDIGSKNVHWYQQKPGQAPVLVIYRDRNRPSGIPERFS GSNSGNTATLTISRAQAGDEADYYCQVWDSNPVVFGGGTKLTVLGQPKANPTVTLFPPSSE ELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQ WKSHRSYSCQVTHEGSTVEKTVAPTECS 65E3 L25 32SYELTQPLSVSVALGQTARITCGGNNIGSKN VHWYQQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDS STVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 67G8 L28 33 SYELTQPLSVSVALGQTARITCGGNNIGSYNVFWYQQKPGQAPVLVIYRDSKRPSGIPERFS GSNSGNTATLTISRAQAGDEADYHCQVWDSSTVVFGGGTKLTVLGQPKANPTVTLFPPSSE ELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQ WKSHRSYSCQVTHEGSTVEKTVAPTECS 65B7v1 L2934 EIVLTQSPGTLSLSPGERATLSCRASQSVSSIY LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSC SFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 65B7v2 L107 1841DVVMTQSPLSLPVTLGQPASISYRSSQSLVYS DGDTYLNWFQQRPGQSPRRLIYKVSNWDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWRGWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK SFNRGEC 63B6 L4 35EIVLTQSPGTLSLSPGERATLSCRASQSVSNS 64D4 YLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGRS FTFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 63F5 L14 36 EVVLTQSPGTLSLSPGERATLSCRASQTVRNNYLAWYQQQPGQAPRLLIFGASSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 65E8 L3 37EIVLTQSPGTLSLSPGERATLSCRASQSVRNS 63H11 YLAWYQQQPGQAPRLLIYGAFSRASGIPDRF64E6 SGSGSGTDFTLTISRLEPEDFAVYYCQQFGSS 67G7LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS 65F11 GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 65C1 L16 38EIVLTQSPGTLSLSPGERATLSCRASQTIRNSY LAWYQQQPGQAPRLLIYGAFSRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQFGSSL TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 66F6 L15 39 EIVLTQSPGTLSLSPGERATLSCRASQSVRNSYLAWYQQQPGQAPRLLIYGAFSRATGIPDRF SGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 64A6 L30 40EILMTQSPATLSVSPGERATLSCRASQSVNSN LAWYQQKPGQAPRLLIYGTSTRATGVPARFGGSGSGTEFTLTISSLQSEDFAFYYCQQYNT WPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 65F9 L31 41EILMTQSPATLSVSPGERATLSCRASQSVSSN LAWYQQKPGQSPRLLIYGASTRATGIPARFGGSGSGTDFTLTISSLQSEDFAFYYCQQYNTW PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 64A7 L17 42 EIVLTQSPGTLSLSPGERATLSCRASQSVSRNYLAWYQQKPGQAPRLLIYGASSRATGVPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSSLCSFGQGTNLDIRRTVAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD YEKHKVYACEVTHQGLSSPVTKSFNRGEC 65C3 L5 43EMVMTQSPATLSVSPGERATLSCRASQSVSS 68D5 QLAWYQEKPGRAPRLLIYGASNRAIDIPARLSGSGSGTEFTLTISSLQSEDFAVYYCQQYNN WPWTFGQGTKVEFKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 67F5 L32 44EIVMTQSPATLSVSPGERVTLSCRASQSVSSN LAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWP WTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 64B10v1 L33 45QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNN 64B10v2 YVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDS SLSAVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 68C8 L34 46QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNN YVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDS SLSAVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 67A5 L35 47DIVMTQTPLSLPVTPGEPASISCRSSQSLLNSD DGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGTGSGTEFTLKISRVEAEDVGVYYC MQRLEFPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 67C10 L36 48DFVMTQTPLSLPVTPGEPASISCRSSQSLLNS DDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYY CMQRIEFPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC 64H6 L37 49SYELTQPLSVSVALGQTARITCGGNNIGSKN VHWYQQKPGQAPVVVIYRDSKRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDS SPVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSP VKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 63F9 L38 50DIQMTQSPSSLSVSVGDRVTITCRASQDIRND LAWYQQTPGKAPKRLIYASSSLQSGVPSRFSGTGSGTEFTLTISSLQPEDFATYFCLQRNSYP LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 67F6v1 L39 51DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSD AGTTYLDWYLQKPGQSPQLLIYTLSFRASGVPDRFSGSGSGTDFTLKITRVEAEDVGVYYCM QRIEFPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 67F6v2 L108 1842DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSD AGTTYLDWYLQKPGRSPQLLIYTLSFRASGVPDRFSGSGSGTDFTLKITRVEAEDVGVYYCM QRIEFPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 48C9 L78 52DIQMTQSPSSLSASIGDRVTITCRASQNIRTYL 49A12 NWYQQKPGKAPKLLIYVASSLESGVPSRFSG51E2 TGSGTDFALTISSLQPEDFATYYCQQSDSIPR TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 48F3 L77 53 DIQMTQSPSSLSASVGDRVTITCRASQRISSYLNWYQQKPGKAPKFLIYAVSSLQSGVPSRFS GSGSGTDFTLTISSLEPEDFATYYCQQSYSATFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 48F8 L49 54EIVLTQSPDFQSVTPKEKVTITCRASQDIGNS 53B9 LHWYQQKPDQSPKLLIKFASQSFSGVPSRFS56B4 GSGSGTDFALTINSLEAEDAATYYCHQSSDL 57E7PLTFGGGTKVDIKRTVAAPSVFIFPPSDEQLK 57F11 SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 48H11 L40 55DIQMTQSPSSLSTSVGDRVTITCRASQNIRSY LNWYQLKPGKAPKVLIYGASNLQSGVPSRFSGSGSGTDFTLTISNLQSEDFAIYYCQQSYNTP CSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 49A10 L65 56DIVMTQTPLSLPVTPGEPASISCRSSQSLLDSD 48D4 DGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQRIEFPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 49C8 L45 57DIQMTQSPSSLSASVGDRVTFTCQASQDINIY 52H1 LNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLP FTFGPGTKVDLKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 49G2 L66 58DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSD 50C12 DGDTYLDWYLQKPGQSPQLLIYTLSYRASG55G11 VPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQHIEFPSTFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 49G3 L47 59DIQMTQSPSSLSASIGDRVTITCQASQGISNYL NWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPL TFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 49H12 L43 60 DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNVVYQQKPGKAPKLLIYDTFILETGVPSRFS GSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 51A8 L61 61NFILTQPHSVSESPGKTVTISCTRSSGSIASDY VQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDR NNHVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADG SPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 51C10.1 L55 62SYELTQPPSVSVSPGQTARITCSGDALPKKYA YWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSISGTMATLTISGAQVEDEADYYCYSTDSSV NHVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 51C10.2 L70 63SYDLTQPPSVSVSPGQTASITCSGDELGDKY ACWYQQKPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDS GTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 51E5 L79 64DIQMTQSPSSLSASVGDRVTITCRASQDIRND LGWYQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYP LTFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 51G2 L51 65 DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYDASSLQSGVPSRFS GSGSGTDFTLTISSLQPEDFATYYCQQTNSFPPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 52A8 L41 66DIQMTQSPSFLSASVGDRVTITCRASQTISSY LNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTP LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 52B8 L82 67 EVVLTQSPATLSVSPGGRATLSCRASQSVSDILAWYQQKPGQAPRLLIYGASTRATGIPARFS GGGSGTEFTLTISSLQSEDFAVYFCQQYNNWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 52C1 L67 68QSVLTQPPSVSAAPGQKVTISCSGSSSNIGINY VSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYCCGTWDSS LSAVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADG SPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 52F8 L42 69DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSN GYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGRGSGTDFSLKISRVEAEDVGIYYCM QALQTPFTFGPGTNVDIKQTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 52H2 L84 70ENVLTQSPGTLSLSPGERATLSCRASQSVRSS YLAWYQQRPGQAPRLLIFGASRRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSS PRSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 53F6 L63 71DIVMTQSPLSLPVTPGEPASISCRSSQSLQHSN GYNYLDWYLQKPGQSPQLLIYLDSNRASGVPDRFSGSGSGTDFTLKISRVEAEDIGVYYCM QGLQTPPTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 53H5.2 L62 72DIQMTQSPSSLSASVGDRVTITCRASQGIRND LGWYQQKPGKAPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHKSYP FTFGPGTKMDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 53H5.3 L80 73EIVMTQSPVTLSVSPGERAIISCRASQSVSSNV AWYQQKPGQTPRLLIYGASTRATGLPTRFSGSGSGTVFTLTISSLQPEDFAVYYCQQFSNSITF GQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 54A1 L44 74 DIQMAQSPSSLSASVGDRVTITCQASQDISIY55G9 LNWYQLKPGKAPKLLIYDVSNLETGVPSRFS GGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 54H10.1 L5375 EIVVTQSPGTLSLSVGERAILSCRASQSFSSSY 55D1LAWYQQKPGQAPRLLIYGASSRATGIPDRFS 48H3 GSGSGTDFTLTISRLEPEDFAVYYCQQYGSSR53C11 TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKVYACEVTHQGLSSPVTKSFNRGEC 55D3 L71 76DIQMTQSPSSLSVSVGDRVTITCRASQDISNY LAWFQQKPGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYP RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 55E4 L75 77DIQMTQSPSSLSTSIGDRITITCRASQSISNYLN 49B11WFQQIPGKAPRLLIYTASSLQSGVPSRFSGSG 50H10 SGTDFTLTISSLQPEDFATYYCQQSSSIPWTF53C1 GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK VYACEVTHQGLSSPVTKSFNRGEC 55E9 L68 78DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSN GFNYLDWYLQKPGQSPQVLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGIYYCM QALQTLITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 55G5 L83 79SYELTQPPSVSVSPGQTASITCSGDNLGDKY AFWYQQKPGQSPVLVIYQDNKRPSGIPERFSGSNSGNTATLTISGTQAVDEADYYCQAWDS ATVIFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSP VKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 56A7 L52 80DIQMTQSPSSVSASVGDRVTITCRASQDISSW 56E4 LAWYQQKPGKAPKFLIYDASTLQSGVPSRFSGSGSGADFTLTINNLQPEDFATYYCQQTNSF PPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 56C11 L64 81SYVLTQPPSVSVAPGQAARITCGGNDIGSKS VHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSKSGNTATLIISRVEAGEEADYYCQVWDS SSDVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADG SPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 56E7 L86 82DLQMTQSPSSLSASVGDRVTITCQASQDIKK FLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILP FTFGPGTTVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 56G1 L76 83 DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWFLQIPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTINSLQPEDFGTYYCQQSSTIPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKVYACEVTHQGLSSPVTKSFNRGEC 56G3.3 L81 84EIVLTQSPGTLSLSPGERATLSCRASQSVSRD 55B10 YLAWYRQKPGQAPRLLVYGASARATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGR SLFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 57B12 L72 85DIQMTQSPSSLSVSVGDRVTITCRASHDISNY LAWFQQKPGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATYYCQQYNTYP RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 57D9 L87 86EIVLTQSPGTLSLSPGERATLSCRASPSVSSSY LAWYQQKPAQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCHQYGTSP CSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 59A10 L48 87DIQMTQSPSSVSASVGDRVTITCRASQGISSW 49H4 LAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTNSFP PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 59C9 L50 88 DIQMTQSPSSVSASVGDRVTITCRASQDIDS58A5 WLVWYQQKPGKAPNLLIYAASNLQRGVPSR 57A4FSGSGSGTDFTLTIASLQPEDFATYYCQQTNS 57F9 FPPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 59G10.2 L60 89SYELSQPPSVSVSPGQTVSITCSGDNLGDKYA CWYQQRPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSS TTWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 59G10.3 L54 90QSVLTQPPSVSAAPGQKVTISCSGSSSNIGDN YVSWYQQFPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDS SLSVMVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 60D7 L69 91DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSD DGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQRIEFPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 60F9 L58 92EIMLTQSPGTLSLSPGERATLSCRASQRVPSS 48B4 YIVWYQQKPGQAPRLLIYGSSNRATGIPDRF52D6 SGSGSGTDFTLTIGRLEPEDFAVYYCQQYGS SPPWTFGQGTKVAIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 60G5.2 L46 93SYELTQPPSVSVSPGQTASITCSGNKLGDKY VCWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQALDEADYYCQAWDS STWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 61G5 L59 94EIMLTQSPGTLSLSPGERATLSCRASQRVPSS YLVWYQQKPGQAPRLLIYGASNRATGIPDRFSGSGSGTDFTLTIGRLEPEDFAVYYCQQYGS SPPWTFGQGTKVAIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 52C5 L73 95DIQMTQSPSSLSASIGDRVTITCRASQSISNYL NWFQQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYCQQSSSIPWTF GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 61H5 L88 96 EIVLTQSPGTLSLSPGERATLSCRASQSVSRD52B9 YLAWYRQKPGQAPRLLIYGASSRATGIPDRF SGSGSGTDFTLTISRLEPEDFAVYYCQQYGRSLFTFGPGTTVDIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC 59D10v1 L5697 SYELTQPPSVSVSPGQTARITCSGDAVPKKY ANWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDSS GNHVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADG SPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 59D10v2 L57 98SYELTQPPSVSVSPGQTASITCSGDKLGDKY VCWYQQMPGQSPVLVIHQNNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDS STAVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGS PVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 56G3.2 L85 99ETVMTQSPATLSVSPGERATLSCRARQSVGS NLIWYQQKPGQAPRLLIFGASSRDTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNW PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 68G5 L13 100 SYELTQPLSVSVALGQTARLTCGGNNIGSINVHWYQQKPGQAPVLVIYRDRNRPSGIPERFS GSNSGNTATLTISRAQAGDEADYYCQLWDSSTVVFGGGTKLTVLGQPKANPTVTLFPPSSE ELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQ WKSHRSYSCQVTHEGSTVEKTVAPTECS 60G5.1 L741843 DIQMTQSPSSLSASIGDRVTITCRASQSISNYL NWFQQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSSIPWT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 48G4 L89 101 EIVLTQSPGTLSLSPGERATLSCRASQSVASS53C3.1 YLVWYQQKPGQAPRLLIYGAFSRATGIPDRF SGSGSGTDFTLTIRRLEPEDFAVYYCQQYGTSPFTFGPGTKVDLKRTVAAPSVFIFPPSDEQL KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD YEKHKVYACEVTHQGLSSPVTKSFNRGEC 50G1 L90102 DIVMTQTPLSLPVSPGEPASISCRSSQSLLDSD DGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSVSGSGTDFTLKISRVEAEDVGVYYC MQRIEFPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 58C2 L91 103EIVMTQTPLSLPVTPGEPASISCRSSQSLFDND DGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQRLEFPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC 50D4 L92 104DIQMTQSPSSLSASVGDRVTITCRASQDISNY LAWYQQKPGKVPTLLIYAASTLLSGVPSRFSGSGSGTDFTLTISSLQPEDVAAYYCQKYYSA PFTFGPGTKVDINRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 50G5v1 L93 105DIQMTQSPSSLSASVGDRVTITCRASQGIRND LGWYQQKPGKAPNRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYP RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 50G5v2 L94 106DVVMTQCPLSLPVTLGQPASISCRSSQRLVY SDGNTYLNWVQQRPGQSPRRLIYKVSNWDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVNY CMEGTHWPRDFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF NRGEC 51C1 L95 107DIQMTQSPSSLSASIGDRVTITCRASQSISNYL NWFQQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSSIPWT FGQGTTVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 53C3.2 L96 108DIVMTQSPATLSVSPGERATLSCRASQSISSN LAWYQQTPGQAPRLLIYGTSIRASTIPARFSGSGSGTEFTLTISSLQSEDFAIYYCHQYTNWPR TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 54H10.3 L97 109DIQMTQSPSSLSASVGDRVTITCRASQTISIYL NWYQQKPGKAPKFLIYSASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFSTYFCQQSYSSPLT FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 55A7 L98 110 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQTYSAPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSG TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKVYACEVTHQGLSSPVTKSFNRGEC 55E6 L99 111EIVLTQSPGTLSLSPGERATLSCRASQSVSRS HLAWYQQNSGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSS PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 61E1 L100 112DIQMTQSPSSLSASIRDRVTITCRASQSIGTFL NWYQQKPGTAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLHPEDFASYYCQQSFSTPLT FGGGTKVEITRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

TABLE 1B Exemplary Antibody Heavy Chain Sequences Contained SEQ ID inClone Designation NO: Amino Acid Sequence 63E6 H6 113QVQLMQSGAEVKKPGASVKVSCKASGYTFTG 66F7 YYMHWVRQAPGQGLEWMGWMNPNSGATKYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTA VYYCARELGDYPFFDYWGQGTLGIVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 66D4 H17114 QVQLVQSGAEVKKPGASVKVSCRASGYTFTG YYIHWMRQAPGHGLEWMGWINPPSGATNYAQKFRGRVAVTRDTSISTVYMELSRLRSDDTAV YYCARETGTWNFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 66B4 H10115 QVQLVQSGAEVKKPGASVKVSCKASGYTFTG YYLHWVRQAPGQGLEWMGWINPNSGGTDYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAV YYCVGDAATGRYYFDNWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK 65B1 H18116 QVQLVQSGAEVKRPGASVKVSCKASGYTFTG YFMHWVRQAPGQGLEWMGWINPNSGATNYAQKFHGRVTMTRDTSITTVYMELSRLRSDDTAV YYCTRELGIFNWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 65B4 H20117 EVQLVESGGGLVQPGGSLRLSCAASGFAFSSY DMHWVRQATGKGLEWVSTIDTAGDAYYPGSVKGRFTISRENAKTSLYLQMNSLRAGDTAVYYC TRDRSSGRFGDFYGMDVWGQGTAVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 67A4H19 118 EVQLEESGGGLVQPGGSLRLSCAASGFTFRTYDMHWVRQVTGKGLEWVSAIGIAGDTYYSDSVK GRFTISRENAKNSLYLQMNSLRVGDTAVYYCARDRSSGRFGDYYGMDVWGQGTTVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 63A10v1 H21 119EVQLVESGGDLVKPGGSLRLSCAVSGITFSNA 63A10v2 WMSWVRQAPGKGLEWVGRIKSKTDGGTTDY63A10v3 AAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTA VYYCTTDSSGSYYVEDYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV HNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK65H11v1 H22 120 EVQLVESGGGLVKPGGSLRLSCAASGFTFSNA 65H11v2WMSWVRQAPGKGLEWVGRIIGKTDGGTTDYA APVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTSDSSGSYYVEDYFDYWGQGTLVAVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 67G10v1 H9 121EVQLVESGGGLVKPGGSLRLACAASGITFNNA 67G10v2 WMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKSILYLQMNSLKSEDTAV YYCTTDSSGSYYVEDYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 64C8H23 122 QVQLVESGGGVVQPGRSLRLSCVASGFTFSSY GMHWVRQDPGKGLEWVAVISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARELLWFGEYGVDHGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK63G8v1 H1 123 QAQLVESGGGVVQPGRSLRLSCAASGFTFSSY 63G8v2GIHWVRQAPGKGLEWVAVISYDGSNKYYADS 63G8v3 VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY68D3v1 CATTVTKEDYYYYGMDVWGQGTTVTVSSAST 64A8KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP 67B4 VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 68D3v2H95 1844 QAQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAFISYAGSNKYYADSVKGRFTISRDNSKNTLYLQMSSLRAEDTA VYYCATTVTEEDYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK66G2 H11 124 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYAD SVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGMDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 65D1 H26 125QVQLVESGGGVVQPGRSLRLSCAASGFTFSYY YIHWVRQAPGKGLEWVALIWYDGSNKDYADSVKGRFTISRDNSKNTLYLHVNSLRAEDTAVYY CAREGTTRRGFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 64H5 H7 126QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAVIWDDGSNKYYADSVKGRFTISRDNSKNTLSLQMNSLRAEDTAVY YCAREYVAEAGFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 65D4 H25127 QEQLVESGGGVVQPGRSLRLSCAVSGFTFSFYG MHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CTRALNWNFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECP PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 65E3 H24 128QVQLVESGGGVVQPGRSLRLSCAASGFTLSNY NMHWVRQAPGKGLEWVAVLWYDGNTKYYADSVKGRVTISRDNSKNTLYLQMNSLRAEDTAV YYCARDVYGDYFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 65G4 H8 129QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAVIWDDGSNKYYADSVKGRFTISRDNSKNTLSLQMNSLRAEDTA VYYCAREYVAEAGFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK 68G5 H12130 QVQLVESGGGVVQPGRSLRLSCTASGFTFSSYG MHWVRQAPGKGLEWVAVIWYDGSNKYHADSVKGRFTISRDDSKNALYLQMNSLRAEDTAVYY CVRDPGYSYGHFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 67G8 H27131 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAVIWYDGSNKDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARSAVALYNWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 65B7v1 H28132 QVQLQESGPGLVNPSQTLSLTCTVSGGSISSDA 65B7v2YYWSWIRQHPGKGLEWIGYIFYSGSTYYNPSL KSRVTISVDTSKNRFSLKLSSVTAADTAVYYCARESRILYFNGYFQHWGQGTLVTVSSASTKGPS VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 63B6 H4 133QVQLQESGPGLVKPSQTLSLTCAVSGGSISSGD 64D4 YYWSWIRQHPGKGLEWIGYIYYSGTTYYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYC ARMTTPYWYFGLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECP PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 63F5 H13 134QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD YYWTWIRQHPGKDLEWITYIYYSGSAYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA RMTTPYWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPP CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREE QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK 63H11 H3 135QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD YYWTWIRQHPGKGLEWIAYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA RMTTPYWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPP CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREE QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK 64E6 H2 136QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD 65E8 YYWTWIRQHPGKGLEWIAYIYYTGSTYYNPSL65F11 KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA 67G7RMTTPYWYFDLWGRGTLVTVSSASTKGPSVFP LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF GTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 65C1 H15 137 QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDYYWTWIRQHPGKGLEWIAYIFYSGSTYYNPSL KSRVTISLDTSKNQFSLKLNSVTAADTAVYYCARMTSPYWYFDLWGRGTLVTVSSASTKGPSVF PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN FGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 66F6 H14 138 QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDYYWTWIRHHPGKGLEWIAYIYYSGSTYYNPSL KSRVTISVDTSKNQFSLKLNSVTAADTAVYYCARMTTPYWYFDLWGRGTLVTVSSASTKGPSVF PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN FGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 64A6 H29 139 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQRPGKGLEWVGYIYYSGGTHYNPS LKSRVTISIDTSENQFSLKLSSVTAADTAVYYCARVLHYSDSRGYSYYSDFWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 65F9 H30 140QVQLQESGPGLVKPSQTLSLTCTLSGGSFSSGD YYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISIDTSKNQFSLKLTSVTAADTAVYYCA RVLHYYDSSGYSYYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 64A7H16 141 QLQLQESGPGLVKPSETLSLTCTVSGGSISSDTSYWGWIRQPPGKGLEWIGNIYYSGTTYFNPSLK SRVSVSVDTSKNQFSLKLSSVTAADTAVFYCARLRGVYWYFDLWGRGTLVTVSSASTKGPSVFP LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF GTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 65C3 H5 142 QVQLQESGPGLVKPSETLSLTCTVSGGSISSYY68D5 WSWIRQPPGKGLEWIGYIYYTGSTNYNPSLKSR VTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTLVTVSSASTKGPSVFPL APCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG TQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 67F5 H31 143 QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTLVTVSSASTKGPSVFPL APCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG TQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 64B10v1 H32 144QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDY YWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARY SSTWDYYYGVDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 64B10v2 H961845 QVQLLESGPGLVKPSETLSLTCTVSGGSVSSGD YYWSWIRQPPGKGLEWIGFIYYSGGTNYNPPLKSRVTISIDTSKNQFSLKLSSVTAADTAVYYCA RYSSTWDYYYGVDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 68C8 H33145 QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGD NYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCG RYRSDWDYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 67A5 H34146 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSY WIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYFCA RRASRGYRFGLAFAIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 67C10 H35147 EVQLVQSGAEVKKPGESLKISCQGSGYSFSSY WIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCA RRASRGYRYGLAFAIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 64H6 H36148 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSY WIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSISTAYLQWNSLKTSDTAMYFC ATVAVSAFNWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 63F9 H37149 QVQLKESGPGLVKPSQTLSLTCTVSGGSISSGG YYWNWIRQHPGKGLEWIGYIYDSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYC ARDVLMVYTKGGYYYYGVDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK67F6v1 H38 150 EVQLVQSGAEVKKPGESLKISCKGSGYSFTGY 67F6v2WIGWVRQLPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISVDKSINTAYLQWSSLKASDTAMYYCARRASRGYSYGHAFDFWGQGTMVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 48C9 H73 151QVQLQQWGAGLLKPSETLSLTCSVYGGSFSGY 49A12 YWTWIRQPPGKGLEWIGEINHSENTNYNPSLKS51E2 RVTISIDTSKNQFSLKLSSVTAADTAVYYCARE SGNFPFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALT SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAP PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFN STFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK 48F3 H72 152QVQLQQWGAGPLKPSETLSLTCAVYGGSISGY YWSWIRQPPGKGLEWIGEITHTGSSNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR GGILWFGEQAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 48F8 H48153 EVQLVESGGGLVKPGGSLRLSCTASGFTFRSYS 53B9MNWVRQAPGKGLEWVSSISSSSSYEYYVDSVK 56B4 GRFTISRDIAKSSLWLQMNSLRAEDTAVYYCA57E7 RSLSIAVAASDYWGKGTLVTVSSASTKGPSVFP 57F11LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPP CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREE QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK 48H11 H39 154QVQLVQSGAEVKKPGASVKVSCKASGYTFTG YYKHWVRQAPGQGLEWMGWINPNSGATKYAQKFQGRVTMTRDTSISTVYMELSRLRSVDTAL YYCAREVPDGIVVAGSNAFDFWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK49A10 H62 155 QVHLVESGGGVVQPGRSLRLSCAASGFTFSNY 48D4GMHWVRQAPGKGLEWVAIIWYDGSNKNYAD SVKGRFTISRDNSKNTLYLEMNSLRAEDTAVYYCARDQDYDFWSGYPYFYYYGMDVWGQGTT VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 49C8 H44 156QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY 52H1 DIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRNTSINTAYMELSSLRSEDTAIY YCARGKEFSRAEFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 49G2 H63157 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNY 50C12GMRWVRQAPGKGLEWVALIWYDGSNKFYAD 55G11 SVKGRFTISRDNSKNTLNLQMNSLRAEDTAVYYCARDRYYDFWSGYPYFFYYGLDVWGQGTTV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 49G3 H46 158QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPR MGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCV RVDTLNYHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 49H12 H42159 QVQLVQSGAEVKKPGASVKVSCMASGYIFTSY DINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRNTSINTAYMELSSLRSEDTAVY YCAKYNWNYGAFDFWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 51A8 H58160 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARADGDYPYYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK51C10.2 H67 161 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYNGSPYDNPSL KRRVTISIDASKNQFSLKLSSMTAADTAVYYCARGALYGMDVWGQGTTVTVSSASTKGPSVFPL APCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG TQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 51E5 H74 162 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKS RVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVTVSSASTKGPSVFPLAP CSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 51G2 H50 163 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSTYIYYADSVK GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDTYISGWNYGMDVWGQGTTVTVSSASTKGP SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 52A8 H40 164 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYA PKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWGQGTLVTVSSASTKGP SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 52B8 H77 165QVQLQESGPGLMKPSETLSLTCTVSGGSISYYY WSWIRQSPGKGLEWIGYIYYSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCASG TRAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF RVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK 52C1 H64 166QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAVIWYDGSNNYYADSVKGRFTISRDNSKSTLFLQMNSLRAEDTAIYY CARDRAGASPGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 52F8 H41167 QVQLVQSGAEVKKPGASVKVSCKASGFTFIGY YTHWVRQAPGQGLEWMGWINPSSGDTKYAQKFQGRVTLARDTSISTAYMELSRLRSDDTAVY YCANSGWYPSYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 52H2H79 168 QVQLQESGPGLVKPSETLSLTCTVSGGSISTYYWSWIRQPPGTGLEWIGYIFYNGNANYSPSLKSR VTFSVDTSKNQFSLKLSSVTAADTAVYFCARETDYGDYARPFEYWGQGTLVTVSSASTKGPSVFP LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF GTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 53F6 H60 169 QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVAVIWYDGSNKYYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGHYDSSGPRDYWGQGTLVTVSSASTKG PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKC KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 53H5.2 H59 170QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGQGLEWVALISYDGSNKYYADSVKGRFTISRDKSKNTLYLQMNSLRAEDTAVY YCAREANWGYNYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 53H5.3H75 171 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYYWNWIRQPPGKGPEWIGEINHSGTTNYNPSLK SRVTISVDTSKNQFSLKLSSVTAADTAVYYCVGILRYFDWLEYYFDYWGQGTLVTVSSASTKGPS VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 54A1 H43 172QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY 55G9 DINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRNTSINTAYMELSSLRSEDTAVY YCAKYNWNYGAFDFWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 54H10.1H52 173 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA 55D1MSWVRQAPGKGLEWVSAISGSGRTTYSADSV 48H3 KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC53C11 AKEQQWLVYFDYWGQGTLVTVSSASTKGPSV FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS NFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 55D3 H68 174QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGV YYWNWIRQHPGKGLEWIGYLYYSGSTYYNPSLKSRLTISADMSKNQFSLKLSSVTVADTAVYY CARDGITMVRGVTHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV HNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK55E4 H70 175 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY 52C5YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS 60G5.1RVTISLDTSNDQFSLRLTSVTAADTAVYYCARV 49B11 TGTDAFDFWGQGTMVTVSSASTKGPSVFPLAP50H10 CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL 53C1TSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 55E9 H65 176 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSFGMHWVRQAPGKGLEWVALIWYDGDNKYYADS VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNSGWDYFYYYGMDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 55G5 H78 177QVQLQESGPGLVKPSETLSLTCTVSGGSISSYY WSWIRQPAGKGLEWIGRIYISGSTNYNPSLENRVTMSGDTSKNQFSLKLNSVTAADTAVYYCAG SGSYSFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALT SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAP PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFN STFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK 50G1 H84 178QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GLHWVRQAPGKGLEWVAVIWNDGSNKLYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARDQYYDFWSGYPYYHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK56A7 H51 179 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS 56E4MNWVRQAPGKGLEWVSSISSSSTYIYYADSVK GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDIYSSGWSYGMDVWGQGTTVTVSSASTKGPS VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 56C11 H61 180QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY GMHWVRQAPGKGLEWVAVIWYDGSYQFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARDHVWRTYRYIFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 56E7H81 181 EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQ GQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLVTVSSASTKGPSVFPLAP CSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 56G1 H71 182 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS RVTISLDTSNKQFSLRLTSVTAADTAVYYCARVTGTDAFDFWGQGTMVTVSSASTKGPSVFPLAP CSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 56G3.3 H76 183 QLQLQESGPGLVKPSETLSLTCTVSGDSISSSSY55B10 YWGWIRQPPGKGLEWIGMIYYSGTTYYNPSLK SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVAAVYWYFDLWGRGTLVTVSSASTKGPSVFPL APCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG TQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 57B12 H69 184 QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGVYYWSWIRQLPGKGLEWIGYIYYSGSTYYNPSL KSRLTISADTSKNQFSLKLSSVTVADTAVYYCARDGITMVRGVTHYYGMDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 57D9 H82 185QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNS ATWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVY YCVGIVVVPAVLFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 58C2 H85186 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNY GMHWVRQAPGKGLEWVAVIWNDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV YYCARDQNYDFWNGYPYYFYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGC LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNT KVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWY VDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 59A10 H47 187 QVQVVESGGGLVKPGGSLRLSCAASGFTFSDS 49H4YMSWIRQAPGKGLEWISSISSSGSIVYFADSVK GRFTISRDIAKNSLYLHMNSLRAEDTAVYYCARETFSSGWFDAFDIWGQGTMVTVSSASTKGPS VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 59C9 H49 188EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS 58A5 MSWVRQAPGKGLEWVSSISSSSTYIYYADSLK57A4 GRFTISRDNAKNSLFLQVNSLRAEDSAVYYCA 57F9RDRWSSGWNEGFDYWGQGTLVTVSSASTKGP SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 59G10.2 H57 189QVQLVESGGGVVQPGRSLRLSCAASGFTFSNY GMHWVRQAPGKGLEWVAITSYGGSNKNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCAREAGYSFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECP PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 59G10.3 H53190 EVQLLGSGGGLVQPGGSLRLSCAASGFTFNHY AMSWVRQAPGKGLEWVSAISGSGAGTFYADSMKGRFTISRDNSENTLHLQMNSLRAEDTAIYY CAKDLRIAVAGSFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK 60D7 H66191 QVQLVESGGGVVQPGRSLRLSCAASGFNFSSY GMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVF YCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK60F9 H55 192 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA 48B4MSWVRQAPGKGLEWVSVISDSGGSTYYADSV 52D6 KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDHSSGWYYYGMDVWGQGTTVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 60G5.2 H45 193QVQLVQSGAEVKTPGASVRVSCKASGYTFTNY GISWVRQAPGQGLEWMGWISAYNGYSNYAQKFQDRVTMTTDTSTSTAYMELRSLRSDDTAVYY CAREEKQLVKDYYYYGMDVWGQGSTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV HNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK61G5 H56 194 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQSPGKGLEWVSVISGSGGDTYYADSV KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDHTSGWYYYGMDVWGQGTTVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 59D10v1 H54 195EVQLLESGGGLVQPGGSLRLSCAASGFTFRNY 59D10v2 AMSWVRQAPGKGLEWVSGISGSSAGTYYADS51C10.1 VKGRFTISRDNSKNTLFLQMDSLRAEDTAVYY CAQDWSIAVAGTFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK 56G3.2 H80196 QVQLQESGPGLVKPSETLSLTCTVSDGSISSYY WNWIRQPAGKGLEWIGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLNLTSVTAADTAVYYCAR GPLWFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALT SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAP PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFN STFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK 48G4 H83 197QVQLVQSGAEVKKPGASVKVSCKVSGYTLTEL 53C3.1 SIHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYC ATHSGSGRFYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 61H5H86 198 QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSY 52B9YWGWIRQPPGKGLEWIGSIYYSGTTYYNPSLK SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVAAVYWYFDLWGRGTLVTVSSASTKGPSVFPL APCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG TQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 50D4 H87 199 QVQLVQSGAEVKKTGASVKVSCKASGYTFTSHDINWVRQATGHGLEWMGWMNPYSGSTGLAQ RFQDRVTMTRNTSISTAYMELSSLRSEDTAVYYCARDLSSGYYYYGLDVWGQGTTVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 50G5v1 H88 200QVQLVQSGAEVKKPGASVKVSCKASGYPFIGY 50G5v2 YMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSITTAYMELSRLRSDDTAVF YCARGGYSYGYEDYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV HNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK51C1 H89 201 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS RVTISLDTSHDQFSLRLTSVTAADTAVYYCARVTGTDAFDFWGQGTMVTVSSASTKGPSVFPLAP CSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 53C3.2 H90 202 QVQLQESGPGLVKPSQTLSLTCTVSNGSINSGNYYWSWIRQHPGKGLEWIGYIYHSGSAYYNPSL KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARTTGASDIWGQGIMVTVSSASTKGPSVFPLAPC SRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT YTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDV SHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGL PAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 54H10.3 H91 203 QVQVVQSGTEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQGLEWMGWINPNSGGTNYA QKFRGRVTMTRDTSISTAYMELSRLRSDDTAVYYCAREEDYSDHHYFDYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 55A7 H92 204QVQLQESGPGLVKPSETLSLTCTVSGGSISSYY WSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLRLSSVTAADTAVYYCARGI TGTIDFWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF RVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK 55E6 H93 205EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYS MNWVRQAPGKGLEWISYISSGSSTIYHADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCA REGYYDSSGYYYNGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 61E1H94 206 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNS AAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITITPDTSKNQFSLQLKSVTPEDTAIY YCAREGSWSSFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK

Each of the exemplary heavy chains (H1, H2, H3 etc.) listed in Table 1B,infra, can be combined with any of the exemplary light chains shown inTable 1A, infra, to form an antibody. Examples of such combinationsinclude H1 combined with any of L1 through L100; H2 combined with any ofL1 through L100; H3 combined with any of L1 through L100, and so on. Insome instances, the antibodies include at least one heavy chain and onelight chain from those listed in Tables 1A and 1B, infra; particularexamples pairings of light chains and heavy chains include L1 with H1,L2 with H1, L3 with H2 or H3, L4 with H4, L5 with H5, L6 with H6, L7with H6, L8 with H7 or H8, L9 with H9, L10 with H9, L11 with H10, L12with H11, L13 with H12, L13 with H14, L14 with H13, L15 with H14, L16with H15, L17 with H16, L18 with H17, L19 with H18, L20 with H19, L21with H20, L22 with H21, L23 with H22, L24 with H23, L25 with H24, L26with H25, L27 with H26, L28 with H27, L29 with H28, L30 with H29, L31with H30, L32 with H31, L33 with H32, L34 with H33, L35 with H34, L36with H35, L37 with H36, L38 with H37, L39 with H38, L40 with H39, L41with H40, L42 with H41, L43 with H42, L44 with H43, L45 with H44, L46with H45, L47 with H46, L48 with H47, L49 with H48, L50 with H49, L51with H50, L52 with H51, L53 with H52, L54 with H53, L55 with H54, andL56 with H54, L57 with H54, L58 with H55, L59 with H56, L60 with H57,L61 with H58, L62 with H59, L63 with H60, L64 with H1, L65 with H62, L66with H63, L67 with H64, L68 with H65, L69 with H66, L70 with H67, L71with H68, L72 with H69, L73 with H70, L74 with H70, and L75 with H70,L76 with H71, L77 with H72, L78 with H73, L79 with H74, L80 with H75,L81 with H76, L82 with H77, L83 with H78, L84 with H79, L85 with H80,L86 with H81, L87 with H82, L88 with H86, L89 with H83, L90 with H84,L91 with H85, L92 with H87, L93 with H88, L94 with H88, L95 with H89,L96 with H90, L97 with H91, L98 with H92, L99 with H93, and L100 withH94. In addition to antigen binding proteins comprising a heavy and alight chain from the same clone, a heavy chain from a first clone can bepaired with a light chain from a second clone (e.g., a heavy chain froma first clone paired with a light chain from a second clone or a heavychain from a first clone paired with a light chain from a second clone).Generally, such pairings can include V_(L) with 90% or greater homologycan be paired with the heavy chain of the naturally occurring clone.

In some instances, the antibodies comprise two different heavy chainsand two different light chains listed in Tables 1A and 1B, infra. Inother instances, the antibodies contain two identical light chains andtwo identical heavy chains. As an example, an antibody orimmunologically functional fragment can include two L1 light chains withtwo H1 heavy chains, two L2 light chains with two H1 heavy chains, twoL3 light chains with two H2 heavy chains or two H3 heavy chains, two L4light chains with two H4 heavy chains, two L5 light chains with two H5heavy chains, two L6 light chains with two H6 heavy chains, two L7 lightchains with two H6 heavy chains, two L8 light chains with two H7 heavychains or two H8 heavy chains, two L9 light chains with two H9 heavychains, two L10 light chains with two H9 heavy chains, two L11 lightchains with two H10 heavy chains, two L12 light chains with two H11heavy chains, two L13 light chains with two H12 heavy chains, two L13light chains with two H14 heavy chains, two L14 light chains with twoH13 heavy chains, two L15 light chains with two H14 heavy chains, twoL16 light chains with two H15 heavy chains, two L17 light chains withtwo H16 heavy chains, two L18 light chains with two H17 heavy chains,two L19 light chains with two H18 heavy chains, two L20 light chainswith two H19 heavy chains, two L21 light chains with two H20 heavychains, two L22 light chains with two H21 heavy chains, two L23 lightchains with two H22 heavy chains, two L24 light chains with two H23heavy chains, two L25 light chains with two H24 heavy chains, two L26light chains with two H25 heavy chains, two L27 light chains with twoH26 heavy chains, two L28 light chains with two H27 heavy chains, twoL29 light chains with two H28 heavy chains, two L30 light chains withtwo H29 heavy chains, two L31 light chains with two H30 heavy chains,two L32 light chains with two H31 heavy chains, two L33 light chainswith two H32 heavy chains, two L34 light chains with two H33 heavychains, two L35 chains with two H34 heavy chains, two L36 chains withtwo H35 heavy chains, two L37 light chains with two H36 heavy chains,two L38 light chains with two H37 heavy chains, two L39 light chainswith two H38 heavy chains, two L40 light chains with two H39 heavychains, two L41 light chains with two H40 heavy chains, two L42 lightchains with two H41 heavy chains, two L43 light chains with two H42heavy chains, two L44 light chains with two H43 heavy chains, two L45light chains with two H44 heavy chains, two L46 light chains with twoH45 heavy chains, two L47 light chains with two H46 heavy chains, twoL48 light chains with two H47 heavy chains, two L49 light chains withtwo H48 heavy chains, two L50 light chains with two H49 heavy chains,two L51 light chains with two H50 heavy chains, two L52 light chainswith two H51 heavy chains, two L53 light chains with two H52 heavychains, two L54 light chains with two H53 heavy chains, two L55 lightchains with two H54 heavy chains, and two L56 light chains with two H54heavy chains, two L57 light chains with two H54 heavy chains, two L58light chains with two H55 heavy chains, two L59 light chains with twoH56 heavy chains, two L60 light chains with two H57 heavy chains, twoL61 light chains with two H58 heavy chains, two L62 light chains withtwo H59 heavy chains, two L63 light chains with two H60 heavy chains,two L64 light chains with two H1 heavy chains, two L65 light chains withtwo H62 heavy chains, two L66 light chains with two H63 heavy chains,two L67 light chains with two H64 heavy chains, two L68 light chainswith two H65 heavy chains, two L69 light chains with two H66 heavychains, two L70 light chains with two H67 heavy chains, two L71 lightchains with two H68 heavy chains, two L72 light chains with two H69heavy chains, two L73 light chains with two H70 heavy chains, two L74light chains with two H70 heavy chains, and two L75 light chains withtwo H70 heavy chains, two L76 light chains with two H71 heavy chains,two L77 light chains with two H72 heavy chains, two L78 light chainswith two H73 heavy chains, two L79 light chains with two H74 heavychains, two L80 light chains with two H75 heavy chains, two L81 lightchains with two H76 heavy chains, two L82 light chains with two H77heavy chains, two L83 light chains with two H78 heavy chains, two L84light chains with two H79 heavy chains, two L85 light chains with twoH80 heavy chains, two L86 light chains with two H81 heavy chains, twoL87 light chains with two H82 heavy chains, two L88 light chains withtwo H86 heavy chains, two L89 light chains with two H83 heavy chains,two L90 light chains with two H84 heavy chains, two L91 light chainswith two H85 heavy chains, two L92 light chains with two H87 heavychains, two L93 light chains with two H88 heavy chains, two L94 lightchains with two H88 heavy chains, two L95 light chains with two H89heavy chains, two L96 light chains with two H90 heavy chains, two L97light chains with two H91 heavy chains, two L98 light chains with twoH92 heavy chains, two L99 light chains with two H93 heavy chains, andtwo L100 light chains with two H94 heavy chains, as well as othersimilar combinations of pairs comprising the light chains and pairs ofheavy chains as listed in Tables 1A and 1B, infra.

In another aspect of the instant disclosure, “hemibodies” are provided.A hemibody is a monovalent antigen binding protein comprising (i) anintact light chain, and (ii) a heavy chain fused to an Fc region (e.g.,an IgG2 Fc region of SEQ ID NO: 11), optionally via a linker, The linkercan be a (G4S)_(x) linker (SEQ ID NO: 207) where “x” is a non-zerointeger (e.g., (G4S)₂, (G4S)₃, (G4S)₄, (G4S)₅, (G4S)₆, (G4S)₇, (G4S)₈,(G4S)₉, (G4S)₁₀; SEQ ID NOs: 208-216, respectively). Hemibodies can beconstructed using the provided heavy and light chain components.

Other antigen binding proteins that are provided are variants ofantibodies formed by combination of the heavy and light chains shown inTables 1A and 1B, infra and comprise light and/or heavy chains that eachhave at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%identity to the amino acid sequences of these chains. In some instances,such antibodies include at least one heavy chain and one light chain,whereas in other instances the variant forms contain two identical lightchains and two identical heavy chains.

Variable Domains of Antigen Binding Proteins

Also provided are antigen binding proteins that contain an antibodyheavy chain variable region selected from the group consisting ofV_(H)1, V_(H)2, V_(H)3, V_(H)4, V_(H)5, V_(H)6, V_(H)7, V_(H)8, V_(H)9,V_(H)10, V_(H)11, V_(H)12, V_(H)13, V_(H)14, V_(H)15, V_(H)16, V_(H)17,V_(H)18, V_(H)19, V_(H)20, V_(H)21 V_(H)22, V_(H)23, V_(H)24, V_(H)25,V_(H)26, V_(H)27, V_(H)28, V_(H)29, V_(H)30, V_(H)31, V_(H)32, V_(H)33,V_(H)34, V_(H)35, V_(H)36, V_(H)37, V_(H)38, V_(H)39, V_(H)40, V_(H)41,V_(H)42, V_(H)43, V_(H)44, V_(H)45, V_(H)46, V_(H)47, V_(H)48, V_(H)49,V_(H)50, V_(H)51, V_(H)52, V_(H)53, V_(H)54, V_(H)55, V_(H)56, V_(H)57,V_(H)58, V_(H)59, V_(H)60, V_(H)61, V_(H)62, V_(H)63, V_(H)64, V_(H)65,V_(H)66, V_(H)67, V_(H)68, V_(H)69, V_(H)70, V_(H)71, V_(H)72, V_(H)73,V_(H)74, V_(H)75, V_(H)76, V_(H)77, V_(H)78, V_(H)79, V_(H)80, 81,V_(H)82, V_(H)83, V_(H)84, V_(H)85, V_(H) 86, V_(H) 87, V_(H)88,V_(H)89, V_(H)90, V_(H)91, V_(H)92, V_(H)93, and V_(H)94 as shown inTable 2B and/or an antibody light chain variable region selected fromthe group consisting of V_(L)1, V_(L)2, V_(L)3, V_(L)4, V_(L)5, V_(L)6,V_(L)7, V_(L)8, V_(L)9, V_(L)10, V_(L)11, V_(L)12, V_(L)13, V_(L)14,V_(L)15, V_(L)16, V_(L)17, V_(L)18, V_(L)19, V_(L)20, V_(L)21, V_(L)22,V_(L)23, V_(L)24, V_(L)25, V_(L)26, V_(L)27, V_(L)28, V_(L)29, V_(L)30,V_(L)31, V_(L)32, V_(L)33, V_(L)34, V_(L)35, V_(L)36, V_(L)37, V_(L)38,V_(L)39, V_(L)40, V_(L)41, V_(L)42, V_(L)43, V_(L)44, V_(L)45, V_(L)46,V_(L)47, V_(L)48, V_(L)49, V_(L)50, V_(L)51, V_(L)52, V_(L)53, V_(L)54,V_(L)55, V_(L)56, V_(L)57, V_(L)58, V_(L)59, V_(L)60, V_(L)61, V_(L)62,V_(L)63, V_(L)64, V_(L)65, V_(L)66, V_(L)67, V_(L)68, V_(L)69, V_(L)70,V_(L)71, V_(L)72, V_(L)73, V_(L)74, V_(L)75, V_(L)76, V_(L)77, V_(L)78,V_(L)79, V_(L)80, V_(L)81, V_(L)82, V_(L)83, V_(L)84, V_(L)85, V_(L)86,V_(L)87, V_(L)88, V_(L)89, V_(L)90, V_(L)91, V_(L)92, V_(L)93, V_(L)94,V_(L)95, V_(L)96, V_(L)97, V_(L)98, V_(L)99 and V_(L)100 as shown inTable 2A, and immunologically functional fragments, derivatives, muteinsand variants of these light chain and heavy chain variable regions.

TABLE 2A Exemplary Antibody Variable Light (V_(L)) Chains Contained SEQID in Clone Designation NO. Amino Acid Sequence 63E6 V_(L)6 217DIQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGKAPNLLIYAASSLQSGVPSRFSGSGSGTDFTLTISGLQPEDFSTYYCQQSYSTSLTFGGGTKVEIKR 66F7 V_(L)7 218DIQMTQSPSSLSASVGDRVTITCRTSQSISNYLNWYQQKPGKAPNLLIYAASSLQSGVPSRFSGSGSGTDFTLTISGLQPEDFSTYYCQQSYSTSLTFGGGTKVEIKR 66D4 V_(L)18 219DIQMTQSPSSLSASVGDRITITCRASQIISRYLNWYQQNPGKAPKLLISAASSLQSGVPSRFSGSGSGPDFTLTISSLQPEDFTTYYCQQSYSSPLTFGGGTKVEVKR 66B4 V_(L)11 220DIQMTQSPSSVSSSVGDRVTITCRASQGISRWLAW YQQKPGKAPKLLIYAASSLKSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGQGTKVEI KR 65B1 V_(L)19 221DIQMTQSPSSLSASVGDRVTITCRASQNINNYLNW YRQKPGKAPELLIYTTSSLQSGVPSRFSGSGSGTDFTLTISSLETEDFETYYCQQSYSTPLTFGGGTKVEIKR 65B4 V_(L)21 222SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVQWY QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTASLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTK LTVLG 67A4 V_(L)20 223SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTK LTVLG 63A10v1 V_(L)22 224SYELTQPHSVSVATAQMARITCGGNNIGSKAVHW YQQKPGQDPVLVIYCDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSD GVFGGGTKLTVLG 63A10v2 V_(L)101 1846SYELTQPHSVSVATAQMARITCGGNNIGSKAVHW YQQKPGQDPVLVIYCDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQAWDSTTV VFGGGTKLTVLG 63A10v3 V_(L)102 1847SYELTQPPSVSVSPGQTANITCSGDKLGNRYTCWY QQKSGQSPVLVIYQDSERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTT VVFGGGTKLTVLG 65H11v1 V_(L)23 225SYELTQPHSVSVATAQMARITCGGNNIGSKTVHW FQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSCDGVFGGGTKLT VLG 65H11v2 V_(L)103 1848SYELTQPPSVSVSPGQTANITCSGDKLGDRYVCWY QQKPGQSPVLVIYQDSKRPSGIPEQFSGSNSGNTATLTISGTQAIDEADYYCQAWDSITVVFGGGTKLTVLG 67G10v1 V_(L)9 226SYELTQPHSVSVATAQMARITCGGNNIGSKAVHW YQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLT VLG 67G10v2 V_(L)10 227SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWY QQKPGQSPVLVIYQDNERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTV LG 64C8 V_(L)24 228DVVMTQSPLSLPVTLGQPASISRRSSPSLVYSDGNT YLNCFQQRPGHSPRRLIYKGSNWDSGVPDRFSGSGSGTDFTLKISRVEAEDVGIYYCIQDTHWPTCSFGQ GTKLEIKR 64A8 V_(L)1 229DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGW 67B4YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE FTLTISTLQPEDFATYSCLQHNSYPLTFGGGTKVEIKR 63G8v1 V_(L)104 1849 DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE FTLTISTLQPDDFATYSCLQHNSYPLTFGGGTKVEIKR 63G8v2 V_(L)105 1850 DIQMTQSPSSLSASVGDRVTITCRASQGIRSGLGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE FTLTVSSLQPEDFATYSCLQHNSYPLTFGGGTKVEIKR 63G8v3 V_(L)106 1851 DIQMTQSPSSLSASVGDRVTITCRASQGIRSGLGWYQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE FTLTVSSLQPEDFATYSCLQHNTYPLTFGGGTKGEIRR 66G2 V_(L)12 230 DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTK FTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR 68D3v1 V_(L)2 231 DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGW 68D3v2YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE FTLTISTLQPDDFATYSCLQHNSYPLTFGGGTKVEIKR 65D1 V_(L)27 232 SYDLTQPPSVSVSPGQTASITCSGDKLGDKYVCWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTAT LTISGIQAMDEADYYCQAWDSRVFGGGTKLTVLG64H5 V_(L)8 233 SYEMTQPLSVSVALGQTARITCGGNNIGSKNVHW 65G4YQQKPGQAPVLVIYRDSKRPSGIPERFSGSNSGNT ATLTISRAQAGDEADYYCQVWDSSSVVFGGGTKLTVLG 65D4 V_(L)26 234 SYELTQPLSVSVALGQTARIPCGGNDIGSKNVHWYQQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTA TLTISRAQAGDEADYYCQVWDSNPVVFGGGTKLTVLG 65E3 V_(L)25 235 SYELTQPLSVSVALGQTARITCGGNNIGSKNVHWYQQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTA TLTISRAQAGDEADYYCQVWDSSTVVFGGGTKLTVLG 68G5 V_(L)13 236 SYELTQPLSVSVALGQTARLTCGGNNIGSINVHWYQQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTA TLTISRAQAGDEADYYCQLWDSSTVVFGGGTKLTVLG 67G8 V_(L)28 237 SYELTQPLSVSVALGQTARITCGGNNIGSYNVFWYQQKPGQAPVLVIYRDSKRPSGIPERFSGSNSGNTAT LTISRAQAGDEADYHCQVWDSSTVVFGGGTKLTVLG 65B7v1 V_(L)29 238 EIVLTQSPGTLSLSPGERATLSCRASQSVSSIYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSCSFGQGTKLEIKR 65B7v2 V_(L)107 1852DVVMTQSPLSLPVTLGQPASISYRSSQSLVYSDGD TYLNWFQQRPGQSPRRLIYKVSNWDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWRGW TFGQGTKVEIKR 63B6 V_(L)4 239EIVLTQSPGTLSLSPGERATLSCRASQSVSNSYLAW 64D4YQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGRSFTFGGGTKVEIRR 63F5 V_(L)14 240EVVLTQSPGTLSLSPGERATLSCRASQTVRNNYLA WYQQQPGQAPRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEI KR 65E8 V_(L)3 241EIVLTQSPGTLSLSPGERATLSCRASQSVRNSYLAW 63H11YQQQPGQAPRLLIYGAFSRASGIPDRFSGSGSGTDF 64E6TLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKR 65F11 67G7 65C1 V_(L)16 242EIVLTQSPGTLSLSPGERATLSCRASQTIRNSYLAW YQQQPGQAPRLLIYGAFSRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKR 66F6 V_(L)15 243EIVLTQSPGTLSLSPGERATLSCRASQSVRNSYLAWYQQQPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKR 64A6 V_(L)30 244EILMTQSPATLSVSPGERATLSCRASQSVNSNLAW YQQKPGQAPRLLIYGTSTRATGVPARFGGSGSGTEFTLTISSLQSEDFAFYYCQQYNTWPWTFGQGTKVE IKR 65F9 V_(L)31 245EILMTQSPATLSVSPGERATLSCRASQSVSSNLAW YQQKPGQSPRLLIYGASTRATGIPARFGGSGSGTDFTLTISSLQSEDFAFYYCQQYNTWPWTFGQGTKVEI KR 64A7 V_(L)17 246EIVLTQSPGTLSLSPGERATLSCRASQSVSRNYLAW YQQKPGQAPRLLIYGASSRATGVPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSSLCSFGQGTNLD IRR 65C3 V_(L)5 247EMVMTQSPATLSVSPGERATLSCRASQSVSSQLA 68D5WYQEKPGRAPRLLIYGASNRAIDIPARLSGSGSGTE FTLTISSLQSEDFAVYYCQQYNNWPWTFGQGTKVEFKR 67F5 V_(L)32 248 EIVMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEF TLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR 64B10v1 V_(L)33 249 QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVA 64B10v2WYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGT SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG 68C8 V_(L)34 250 QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG 67A5 V_(L)35 251 DIVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGT GSGTEFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR 67C10 V_(L)36 252 DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGS GSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR 64H6 V_(L)37 253 SYELTQPLSVSVALGQTARITCGGNNIGSKNVHWYQQKPGQAPVVVIYRDSKRPSGIPERFSGSNSGNTA TLTISRAQAGDEADYYCQVWDSSPVVFGGGTKLTVLG 63F9 V_(L)38 254 DIQMTQSPSSLSVSVGDRVTITCRASQDIRNDLAWYQQTPGKAPKRLIYASSSLQSGVPSRFSGTGSGTEFTLTISSLQPEDFATYFCLQRNSYPLTFGGGTKVEIKR 67F6v1 V_(L)39 255DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSDAGTTYLDWYLQKPGQSPQLLIYTLSFRASGVPDRFSGSG SGTDFTLKITRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR 67F6v2 V_(L)108 1853 DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSDAGTTYLDWYLQKPGRSPQLLIYTLSFRASGVPDRFSGSG SGTDFTLKITRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR 48C9 V_(L)78 256 DIQMTQSPSSLSASIGDRVTITCRASQNIRTYLNWY 49A12QQKPGKAPKLLIYVASSLESGVPSRFSGTGSGTDF 51E2ALTISSLQPEDFATYYCQQSDSIPRTFGQGTKVEIKR 48F3 V_(L)77 257DIQMTQSPSSLSASVGDRVTITCRASQRISSYLNWYQQKPGKAPKFLIYAVSSLQSGVPSRFSGSGSGTDFTLTISSLEPEDFATYYCQQSYSATFTFGPGTKVDIKR 48F8 V_(L)49 258EIVLTQSPDFQSVTPKEKVTITCRASQDIGNSLHWY 53B9QQKPDQSPKLLIKFASQSFSGVPSRFSGSGSGTDFA 56B4LTINSLEAEDAATYYCHQSSDLPLTFGGGTKVDIKR 57E7 57F11 48H11 V_(L)40 259DIQMTQSPSSLSTSVGDRVTITCRASQNIRSYLNWY QLKPGKAPKVLIYGASNLQSGVPSRFSGSGSGTDFTLTISNLQSEDFAIYYCQQSYNTPCSFGQGTKLEIKR 49A10 V_(L)65 260DIVMTQTPLSLPVTPGEPASISCRSSQSLLDSDDGN 48D4TYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGS GSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR 49C8 V_(L)45 261 DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNW 52H1YQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTD FTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR 49G2 V_(L)66 262 DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDT 50C12YLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSG 55G11SGTDFTLKISRVEAEDVGVYYCMQHIEFPSTFGQG TRLEIKR 49G3 V_(L)47 263DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWY QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR 49H12 V_(L)43 264DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNW YQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR 51A8 V_(L)61 265NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNS ASLTISGLKTEDEADYYCQSYDRNNHVVFGGGTKLTVLG 51C10.1 V_(L)55 266 SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSISGTMAT LTISGAQVEDEADYYCYSTDSSVNHVVFGGGTKLTVLG 51C10.2 V_(L)70 267 SYDLTQPPSVSVSPGQTASITCSGDELGDKYACWYQQKPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTAT LTISGTQAMDEADYYCQAWDSGTVVFGGGTKLTVLG 51E5 V_(L)79 268 DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTE FTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR 51G2 V_(L)51 269 DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQTNSFPPWTFGQGTKVEIKR 52A8 V_(L)41 270 DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR 52B8 V_(L)82 271EVVLTQSPATLSVSPGGRATLSCRASQSVSDILAW YQQKPGQAPRLLIYGASTRATGIPARFSGGGSGTEFTLTISSLQSEDFAVYFCQQYNNWPLTFGGGTKVE IKR 52C1 V_(L)67 272QSVLTQPPSVSAAPGQKVTISCSGSSSNIGINYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSA TLGITGLQTGDEADYCCGTWDSSLSAVVFGGGTKLTVLG 52F8 V_(L)42 273 DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGR GSGTDFSLKISRVEAEDVGIYYCMQALQTPFTFGPGTNVDIKQ 52H2 V_(L)84 274 ENVLTQSPGTLSLSPGERATLSCRASQSVRSSYLAWYQQRPGQAPRLLIFGASRRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPRSFGQGTKLEIKR 53F6 V_(L)63 275 DIVMTQSPLSLPVTPGEPASISCRSSQSLQHSNGYNYLDWYLQKPGQSPQLLIYLDSNRASGVPDRFSGSG SGTDFTLKISRVEAEDIGVYYCMQGLQTPPTFGGGTKVEIKR 53H5.2 V_(L)62 276 DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASSLQSGVPSRFSGSGSGTE FTLTISSLQPEDFATYYCLQHKSYPFTFGPGTKMDIKG 53H5.3 V_(L)80 277 EIVMTQSPVTLSVSPGERAIISCRASQSVSSNVAWYQQKPGQTPRLLIYGASTRATGLPTRFSGSGSGTVFT LTISSLQPEDFAVYYCQQFSNSITFGQGTRLEIKR54A1 V_(L)44 278 DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWY 55G9QLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR 54H10.1 V_(L)53 279EIVVTQSPGTLSLSVGERAILSCRASQSFSSSYLAW 55D1YQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDF 48H3TLTISRLEPEDFAVYYCQQYGSSRTFGQGTKVEIKR 53C11 55D3 V_(L)71 280DIQMTQSPSSLSVSVGDRVTITCRASQDISNYLAWFQQKPGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPRTFGQGTKVEIKR 55E4 V_(L)75 281DIQMTQSPSSLSTSIGDRITITCRASQSISNYLNWFQ 49B11QIPGKAPRLLIYTASSLQSGVPSRFSGSGSGTDFTLT 50H10ISSLQPEDFATYYCQQSSSIPWTFGQGTKVEIKR 53C1 55E9 V_(L)68 282DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGFN YLDWYLQKPGQSPQVLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGIYYCMQALQTLITFGQ GTRLEIKR 55G5 V_(L)83 283SYELTQPPSVSVSPGQTASITCSGDNLGDKYAFWY QQKPGQSPVLIYQDNKRPSGIPERFSGSNSGNTATLTISGTQAVDEADYYCQAWDSATVIFGGGTKLTV LG 56A7 V_(L)52 284DIQMTQSPSSVSASVGDRVTITCRASQDISSWLAW 56E4YQQKPGKAPKFLIYDASTLQSGVPSRFSGSGSGAD FTLTINNLQPEDFATYYCQQTNSFPPWTFGQGTKVEIKR 56C11 V_(L)64 285 SYVLTQPPSVSVAPGQAARITCGGNDIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSKSGNTA TLIISRVEAGEEADYYCQVWDSSSDVVFGGGTKLTVLG 56E7 V_(L)86 286 DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR 56G1 V_(L)76 287DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWFLQIPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTINSLQPEDFGTYYCQQSSTIPWTFGQGTKVEIKR 56G3.3 V_(L)81 288EIVLTQSPGTLSLSPGERATLSCRASQSVSRDYLAW 55B10YRQKPGQAPRLLVYGASARATGIPDRFSGSGSGTD FTLTISRLEPEDFAVYYCQQYGRSLFTFGPGTKVDIKR 57B12 V_(L)72 289 DIQMTQSPSSLSVSVGDRVTITCRASHDISNYLAWFQQKPGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATYYCQQYNTYPRTFGQGTKVEIKR 57D9 V_(L)87 290EIVLTQSPGTLSLSPGERATLSCRASPSVSSSYLAWYQQKPAQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCHQYGTSPCSFGQGTKLEIKR 59A10 V_(L)48 291DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAW 49H4YQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQTNSFPPWTFGQGTKVEIKR 59C9 V_(L)50 292 DIQMTQSPSSVSASVGDRVTITCRASQDIDSWLVW 58A5YQQKPGKAPNLLIYAASNLQRGVPSRFSGSGSGTD 57A4FTLTIASLQPEDFATYYCQQTNSFPPWTFGQGTKV 57F9 EIKR 59G10.2 V_(L)60 293SYELSQPPSVSVSPGQTVSITCSGDNLGDKYACWY QQRPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTTWVFGGGTKL TVLG 59G10.3 V_(L)54 294QSVLTQPPSVSAAPGQKVTISCSGSSSNIGDNYVS WYQQFPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSVMVFGGG TKLTVLG 60D7 V_(L)69 295DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSG SGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR 60F9 V_(L)58 296 EIMLTQSPGTLSLSPGERATLSCRASQRVPSSYIVW 48B4YQQKPGQAPRLLIYGSSNRATGIPDRFSGSGSGTDF 52D6TLTIGRLEPEDFAVYYCQQYGSSPPWTFGQGTKVA IKR 60G5.2 V_(L)46 297SYELTQPPSVSVSPGQTASITCSGNKLGDKYVCWY QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQALDEADYYCQAWDSSTWVFGGGTKLTV LG 61G5 V_(L)59 298EIMLTQSPGTLSLSPGERATLSCRASQRVPSSYLVW YQQKPGQAPRLLIYGASNRATGIPDRFSGSGSGTDFTLTIGRLEPEDFAVYYCQQYGSSPPWTFGQGTKV AIKR 52C5 V_(L)73 299DIQMTQSPSSLSASIGDRVTITCRASQSISNYLNWFQQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYCQQSSSIPWTFGQGTKVEIKR 61H5 V_(L)88 300EIVLTQSPGTLSLSPGERATLSCRASQSVSRDYLAW 52B9YRQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGRSLFTFGPGTTVDIKR 59D10v1 V_(L)56 301SYELTQPPSVSVSPGQTARITCSGDAVPKKYANWY QQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDSSGNHVVFGGGTKL TVLG 59D10v2 V_(L)57 302SYELTQPPSVSVSPGQTASITCSGDKLGDKYVCWY QQMPGQSPVLVIHQNNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTAVFGGGTKLT VLG 56G3.2 V_(L)85 303ETVMTQSPATLSVSPGERATLSCRARQSVGSNLIW YQQKPGQAPRLLIFGASSRDTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPLTFGGGTKVEI KR 48G4 V_(L)89 304EIVLTQSPGTLSLSPGERATLSCRASQSVASSYLVW 53C3.1YQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDF TLTIRRLEPEDFAVYYCQQYGTSPFTFGPGTKVDLKR 50G1 V_(L)90 305 DIVMTQTPLSLPVSPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSVS GSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR 58C2 V_(L)91 306 EIVMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGS GSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR 60G5.1 V_(L)74 1854 DIQMTQSPSSLSASIGDRVTITCRASQSISNYLNWFQQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSSIPWTFGQGTKVEIKR 50D4 V_(L)92 307DIQMTQSPSSLSASVGDRVTITCRASQDISNYLAW YQQKPGKVPTLLIYAASTLLSGVPSRFSGSGSGTDFTLTISSLQPEDVAAYYCQKYYSAPFTFGPGTKVDI NR 50G5 v1 V_(L)93 308DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW YQQKPGKAPNRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPRTFGQGTKVEI KR 50G5 v2 V_(L)94 309DVVMTQCPLSLPVTLGQPASISCRSSQRLVYSDGN TYLNWVQQRPGQSPRRLIYKVSNWDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVNYCMEGTHWPRDF GQGTRLEIKR 51C1 V_(L)95 310DIQMTQSPSSLSASIGDRVTITCRASQSISNYLNWFQQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSSIPWTFGQGTTVEIKR 53C3.2 V_(L)96 311DIVMTQSPATLSVSPGERATLSCRASQSISSNLAWYQQTPGQAPRLLIYGTSIRASTIPARFSGSGSGTEFTLTISSLQSEDFAIYYCHQYTNWPRTFGQGTKVEIKR 54H10.3 V_(L)97 312DIQMTQSPSSLSASVGDRVTITCRASQTISIYLNWYQQKPGKAPKFLIYSASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFSTYFCQQSYSSPLTFGGGTKVEIKR 55A7 V_(L)98 313DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPFTFGPGTKVDIKR 55E6 V_(L)99 314EIVLTQSPGTLSLSPGERATLSCRASQSVSRSHLAWYQQNSGQAPRLLIYGASSRATGIPDRFSGSGSGTDF TLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKR 61E1 V_(L)100 315 DIQMTQSPSSLSASIRDRVTITCRASQSIGTFLNWYQQKPGTAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLHPEDFASYYCQQSFSTPLTFGGGTKVEITR

TABLE 2B Exemplary Antibody Variable Heavy (V_(H)) Chains Contained SEQID in Clone Designation NO. Amino Acid Sequence 63E6 V_(H) 6 316QVQLMQSGAEVKKPGASVKVSCKASGYTFTGY 66F7 YMHWVRQAPGQGLEWMGWMNPNSGATKYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVY YCARELGDYPFFDYWGQGTLGIVSS 66D4 V_(H)17317 QVQLVQSGAEVKKPGASVKVSCRASGYTFTGY YIHWMRQAPGHGLEWMGWINPPSGATNYAQKFRGRVAVTRDTSISTVYMELSRLRSDDTAVYYC ARETGTWNFFDYWGQGTLVTVSS 66B4 V_(H)10318 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY YLHWVRQAPGQGLEWMGWINPNSGGTDYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYC VGDAATGRYYFDNWGQGTLVTVSS 65B1 V_(H)18319 QVQLVQSGAEVKRPGASVKVSCKASGYTFTGY FMHWVRQAPGQGLEWMGWINPNSGATNYAQKFHGRVTMTRDTSITTVYMELSRLRSDDTAVY YCTRELGIFNWFDPWGQGTLVTVSS 65B4 V_(H)20320 EVQLVESGGGLVQPGGSLRLSCAASGFAFSSYD MHWVRQATGKGLEWVSTIDTAGDAYYPGSVKGRFTISRENAKTSLYLQMNSLRAGDTAVYYCTR DRSSGRFGDFYGMDVWGQGTAVTVSS 67A4V_(H)19 321 EVQLEESGGGLVQPGGSLRLSCAASGFTFRTYDMHWVRQVTGKGLEWVSAIGIAGDTYYSDSVK GRFTISRENAKNSLYLQMNSLRVGDTAVYYCARDRSSGRFGDYYGMDVWGQGTTVTVSS 63A10v1 V_(H)21 322EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAW 63A10v2MSWVRQAPGKGLEWVGRIKSKTDGGTTDYAA 63A10v3 PVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYFDYWGQGTLVTVSS 65H11v1 V_(H)22 323EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAW 65H11v2MSWVRQAPGKGLEWVGRIIGKTDGGTTDYAAP VKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTSDSSGSYYVEDYFDYWGQGTLVAVSS 67G10v1 V_(H)9 324EVQLVESGGGLVKPGGSLRLACAASGITFNNA 67G10v2 WMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKSILYLQMNSLKSEDTAVY YCTTDSSGSYYVEDYFDYWGQGTLVTVSS 64C8V_(H)23 325 QVQLVESGGGVVQPGRSLRLSCVASGFTFSSYGMHWVRQDPGKGLEWVAVISYDGSNKHYADSV KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARELLWFGEYGVDHGMDVWGQGTTVTVSS 63G8v1 V_(H)1 326QAQLVESGGGVVQPGRSLRLSCAASGFTFSSYG 63G8v2IHWVRQAPGKGLEWVAVISYDGSNKYYADSVK 63G8v3GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAT 68D3v1 TVTKEDYYYYGMDVWGQGTTVTVSS 64A867B4 68D3v2 V_(H)95 1855 QAQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFISYAGSNKYY ADSVKGRFTISRDNSKNTLYLQMSSLRAEDTAVYYCATTVTEEDYYYYGMDVWGQGTTVT VSS 66G2 V_(H)11 327QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCA TTVTKEDYYYYGMDVWGQGTTVTVSS 65D1V_(H)26 328 QVQLVESGGGVVQPGRSLRLSCAASGFTFSYYYIHWVRQAPGKGLEWVALIWYDGSNKDYADSV KGRFTISRDNSKNTLYLHVNSLRAEDTAVYYCAREGTTRRGFDYWGQGTLVTVSS 64H5 V_(H)7 329 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWDDGSNKYYADS VKGRFTISRDNSKNTLSLQMNSLRAEDTAVYYCAREYVAEAGFDYWGQGTLVTVSS 65D4 V_(H)25 330QEQLVESGGGVVQPGRSLRLSCAVSGFTFSFYG MHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CTRALNWNFFDYWGQGTLVTVSS 65E3 V_(H)24331 QVQLVESGGGVVQPGRSLRLSCAASGFTLSNYN MHWVRQAPGKGLEWVAVLWYDGNTKYYADSVKGRVTISRDNSKNTLYLQMNSLRAEDTAVYY CARDVYGDYFAYWGQGTLVTVSS 65G4 V_(H)8 332QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVIWDDGSNKYYADSVKGRFTISRDNSKNTLSLQMNSLRAEDTAV YYCAREYVAEAGFDYWGQGTLVTVSS 68G5V_(H)12 333 QVQLVESGGGVVQPGRSLRLSCTASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYHADS VKGRFTISRDDSKNALYLQMNSLRAEDTAVYYCVRDPGYSYGHFDYWGQGTLVTVSS 67G8 V_(H)27 334QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVIWYDGSNKDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CARSAVALYNWFDPWGQGTLVTVSS 65B7v1V_(H)28 335 QVQLQESGPGLVNPSQTLSLTCTVSGGSISSDAY 65B7v2YWSWIRQHPGKGLEWIGYIFYSGSTYYNPSLKS RVTISVDTSKNRFSLKLSSVTAADTAVYYCARESRILYFNGYFQHWGQGTLVTVSS 63B6 V_(H)4 336QVQLQESGPGLVKPSQTLSLTCAVSGGSISSGDY 64D4YWSWIRQHPGKGLEWIGYIYYSGTTYYNPSLKS RVTISVDTSKNQFSLKLTSVTAADTAVYYCARMTTPYWYFGLWGRGTLVTVSS 63F5 V_(H)13 337 QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDYYWTWIRQHPGKDLEWITYIYYSGSAYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYCARMTTPYWYFDLWGRGTLVTVSS 63H11 V_(H)3 338 QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDYYWTWIRQHPGKGLEWIAYIYYSGSTYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYCARMTTPYWYFDLWGRGTLVTVSS 65E8 V_(H)2 339 QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY64E6 YWTWIRQHPGKGLEWIAYIYYTGSTYYNPSLKS 65F11RVTISVDTSKNQFSLKLSSVTAADTAVYYCARM 67G7 TTPYWYFDLWGRGTLVTVSS 65C1 V_(H)15340 QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY YWTWIRQHPGKGLEWIAYIFYSGSTYYNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYYCARM TSPYWYFDLWGRGTLVTVSS 66F6 V_(H)14 341QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY YWTWIRHHPGKGLEWIAYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLNSVTAADTAVYYCAR MTTPYWYFDLWGRGTLVTVSS 64A6 V_(H)29 342QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGY YWSWIRQRPGKGLEWVGYIYYSGGTHYNPSLKSRVTISIDTSENQFSLKLSSVTAADTAVYYCARV LHYSDSRGYSYYSDFWGQGTLVTVSS 65F9V_(H)30 343 QVQLQESGPGLVKPSQTLSLTCTLSGGSFSSGDYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKS RVTISIDTSKNQFSLKLTSVTAADTAVYYCARVLHYYDSSGYSYYFDYWGQGTLVTVSS 64A7 V_(H)16 344QLQLQESGPGLVKPSETLSLTCTVSGGSISSDTS YWGWIRQPPGKGLEWIGNIYYSGTTYFNPSLKSRVSVSVDTSKNQFSLKLSSVTAADTAVFYCARL RGVYWYFDLWGRGTLVTVSS 65C3 V_(H)5 345QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYW 68D5SWIRQPPGKGLEWIGYIYYTGSTNYNPSLKSRV TISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTLVTVSS 67F5 V_(H)31 346 QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRV TISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTLVTVSS 64B10v1 V_(H)32 347QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDY YWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARY SSTWDYYYGVDVWGQGTTVTVSS 64B10v2V_(H)96 1856 QVQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPPLK SRVTISIDTSKNQFSLKLSSVTAADTAVYYCARYSSTWDYYYGVDVWGQGTTVTVSS 68C8 V_(H)33 348QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGD NYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCG RYRSDWDYYYGMDVWGQGTTVTVSS 67A5 V_(H)34349 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYW IGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYFCARR ASRGYRFGLAFAIWGQGTMVTVSS 67C10 V_(H)35350 EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYW IGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARR ASRGYRYGLAFAIWGQGTMVTVSS 64H6 V_(H)36351 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYW IGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSISTAYLQWNSLKTSDTAMYFCATV AVSAFNWFDPWGQGTLVTVSS 63F9 V_(H)37 352QVQLKESGPGLVKPSQTLSLTCTVSGGSISSGGY YWNWIRQHPGKGLEWIGYIYDSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCAR DVLMVYTKGGYYYYGVDVWGQGTTVTVSS 67F6v1V_(H)38 353 EVQLVQSGAEVKKPGESLKISCKGSGYSFTGYW 67F6v2IGWVRQLPGKGLEWMGIIYPGDSDTRYSPSFQG QVTISVDKSINTAYLQWSSLKASDTAMYYCARRASRGYSYGHAFDFWGQGTMVTVSS 48C9 V_(H)73 354QVQLQQWGAGLLKPSETLSLTCSVYGGSFSGY 49A12 YWTWIRQPPGKGLEWIGEINHSENTNYNPSLKS51E2 RVTISIDTSKNQFSLKLSSVTAADTAVYYCARES GNFPFDYWGQGTLVTVSS 48F3 V_(H)72355 QVQLQQWGAGPLKPSETLSLTCAVYGGSISGYY WSWIRQPPGKGLEWIGEITHTGSSNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGG ILWFGEQAFDIWGQGTMVTVSS 48F8 V_(H)48356 EVQLVESGGGLVKPGGSLRLSCTASGFTFRSYS 53B9MNWVRQAPGKGLEWVSSISSSSSYEYYVDSVK 56B4 GRFTISRDIAKSSLWLQMNSLRAEDTAVYYCAR57E7 SLSIAVAASDYWGKGTLVTVSS 57F11 48H11 V_(H)39 357QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY YKHWVRQAPGQGLEWMGWINPNSGATKYAQKFQGRVTMTRDTSISTVYMELSRLRSVDTALYY CAREVPDGIVVAGSNAFDFWGQGTMVTVSS 49A10V_(H)62 358 QVHLVESGGGVVQPGRSLRLSCAASGFTFSNYG 48D4MHWVRQAPGKGLEWVAIIWYDGSNKNYADSV KGRFTISRDNSKNTLYLEMNSLRAEDTAVYYCARDQDYDFWSGYPYFYYYGMDVWGQGTTVTVSS 49C8 V_(H)44 359QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY 52H1 DIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRNTSINTAYMELSSLRSEDTAIYY CARGKEFSRAEFDYWGQGTLVTVSS 49G2 V_(H)63360 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYG 50C12MRWVRQAPGKGLEWVALIWYDGSNKFYADSV 55G11 KGRFTISRDNSKNTLNLQMNSLRAEDTAVYYCARDRYYDFWSGYPYFFYYGLDVWGQGTTVTV SS 49G3 V_(H)46 361QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRM GVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRV DTLNYHYYGMDVWGQGTTVTVSS 49H12 V_(H)42362 QVQLVQSGAEVKKPGASVKVSCMASGYIFTSY DINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRNTSINTAYMELSSLRSEDTAVYY CAKYNWNYGAFDFWGQGTMVTVSS 51A8 V_(H)58363 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARADGDYPYYYYYYGMDVWGQGTTVTVSS 51C10.1V_(H)54 364 EVQLLESGGGLVQPGGSLRLSCAASGFTFRNYA 59D10v1MSWVRQAPGKGLEWVSGISGSSAGTYYADSVK 59D10v2GRFTISRDNSKNTLFLQMDSLRAEDTAVYYCAQ DWSIAVAGTFDYWGQGTLVTVSS 51C10.2V_(H)67 365 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYNGSPYDNPSLK RRVTISIDASKNQFSLKLSSMTAADTAVYYCARGALYGMDVWGQGTTVTVSS 51E5 V_(H)74 366 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKS RVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVTVSS 51G2 V_(H)50 367 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSTYIYYADSVK GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDTYISGWNYGMDVWGQGTTVTVSS 52A8 V_(H)40 368QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY YLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYC AREGGTYNWFDPWGQGTLVTVSS 52B8 V_(H)77369 QVQLQESGPGLMKPSETLSLTCTVSGGSISYYY WSWIRQSPGKGLEWIGYIYYSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCASG TRAFDIWGQGTMVTVSS 52C1 V_(H)64 370QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVIWYDGSNNYYADSVKGRFTISRDNSKSTLFLQMNSLRAEDTAIYYC ARDRAGASPGMDVWGQGTTVTVSS 52F8 V_(H)41371 QVQLVQSGAEVKKPGASVKVSCKASGFTFIGY YTHWVRQAPGQGLEWMGWINPSSGDTKYAQKFQGRVTLARDTSISTAYMELSRLRSDDTAVYYC ANSGWYPSYYYGMDVWGQGTTVTVSS 52H2V_(H)79 372 QVQLQESGPGLVKPSETLSLTCTVSGGSISTYYWSWIRQPPGTGLEWIGYIFYNGNANYSPSLKSR VTFSVDTSKNQFSLKLSSVTAADTAVYFCARETDYGDYARPFEYWGQGTLVTVSS 53F6 V_(H)60 373QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYG MHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CARGHYDSSGPRDYWGQGTLVTVSS 53H5.2V_(H)59 374 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGQGLEWVALISYDGSNKYYADSV KGRFTISRDKSKNTLYLQMNSLRAEDTAVYYCAREANWGYNYYGMDVWGQGTTVTVSS 53H5.3 V_(H)75 375QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDY YWNWIRQPPGKGPEWIGEINHSGTTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVGI LRYFDWLEYYFDYWGQGTLVTVSS 54A1 V_(H)43376 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY 55G9 DINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRNTSINTAYMELSSLRSEDTAVYY CAKYNWNYGAFDFWGQGTMVTVSS 54H10.1V_(H)52 377 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA 55D1MSWVRQAPGKGLEWVSAISGSGRTTYSADSVK 48H3 GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA53C11 KEQQWLVYFDYWGQGTLVTVSS 55D3 V_(H)68 378QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGVY YWNWIRQHPGKGLEWIGYLYYSGSTYYNPSLKSRLTISADMSKNQFSLKLSSVTVADTAVYYCAR DGITMVRGVTHYYGMDVWGQGTTVTVSS 55E4V_(H)70 379 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY 49B11YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS 50H10RVTISLDTSNDQFSLRLTSVTAADTAVYYCARV 53C1 TGTDAFDFWGQGTMVTVSS 52C5 60G5.155E9 V_(H)65 380 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSFGMHWVRQAPGKGLEWVALIWYDGDNKYYADS VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNSGWDYFYYYGMDVWGQGTTVTVSS 55G5 V_(H)78 381QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYW SWIRQPAGKGLEWIGRIYISGSTNYNPSLENRVTMSGDTSKNQFSLKLNSVTAADTAVYYCAGSGS YSFDYWGQGTLVTVSS 50G1 V_(H)84 382QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG LHWVRQAPGKGLEWVAVIWNDGSNKLYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDQYYDFWSGYPYYHYYGMDVWGQGTTVT VSS 56A7V_(H)51 383 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS 56E4MNWVRQAPGKGLEWVSSISSSSTYIYYADSVK GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDIYSSGWSYGMDVWGQGTTVTVSS 56C11 V_(H)61 384QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVIWYDGSYQFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CARDHVWRTYRYIFDYWGQGTLVTVSS 56E7V_(H)81 385 EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQG QVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLVTVSS 56G1 V_(H)71 386 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS RVTISLDTSNKQFSLRLTSVTAADTAVYYCARVTGTDAFDFWGQGTMVTVSS 56G3.3 V_(H)76 387QLQLQESGPGLVKPSETLSLTCTVSGDSISSSSY 55B10YWGWIRQPPGKGLEWIGMIYYSGTTYYNPSLK SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVAAVYWYFDLWGRGTLVTVSS 57B12 V_(H)69 388QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGVY YWSWIRQLPGKGLEWIGYIYYSGSTYYNPSLKSRLTISADTSKNQFSLKLSSVTVADTAVYYCARD GITMVRGVTHYYGMDVWGQGTTVTVSS 57D9V_(H)82 389 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSATWNWIRQSPSRGLEWLGRTYYRSKWYNDYAV SVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCVGIVVVPAVLFDYWGQGTLVTVSS 58C2 V_(H)85 390QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYG MHWVRQAPGKGLEWVAVIWNDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CARDQNYDFWNGYPYYFYYGMDVWGQGTTV TVSS59A10 V_(H)47 391 QVQVVESGGGLVKPGGSLRLSCAASGFTFSDSY 49H4MSWIRQAPGKGLEWISSISSSGSIVYFADSVKGR FTISRDIAKNSLYLHMNSLRAEDTAVYYCARETFSSGWFDAFDIWGQGTMVTVSS 59C9 V_(H)49 392EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS 58A5 MSWVRQAPGKGLEWVSSISSSSTYIYYADSLKG57A4 RFTISRDNAKNSLFLQVNSLRAEDSAVYYCARD 57F9 RWSSGWNEGFDYWGQGTLVTVSS59G10.2 V_(H)57 393 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAITSYGGSNKNYADSV KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREAGYSFDYWGQGTLVTVSS 59G10.3 V_(H)53 394EVQLLGSGGGLVQPGGSLRLSCAASGFTFNHYA MSWVRQAPGKGLEWVSAISGSGAGTFYADSMKGRFTISRDNSENTLHLQMNSLRAEDTAIYYCA KDLRIAVAGSFDYWGQGTLVTVSS 60D7 V_(H)66395 QVQLVESGGGVVQPGRSLRLSCAASGFNFSSYG MHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYC ARDQYFDFWSGYPFFYYYGMDVWGQGTTVTV SS60F9 V_(H)55 396 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA 48B4MSWVRQAPGKGLEWVSVISDSGGSTYYADSVK 52D6 GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDHSSGWYYYGMDVWGQGTTVTVSS 60G5.2 V_(H)45 397QVQLVQSGAEVKTPGASVRVSCKASGYTFTNY GISWVRQAPGQGLEWMGWISAYNGYSNYAQKFQDRVTMTTDTSTSTAYMELRSLRSDDTAVYY CAREEKQLVKDYYYYGMDVWGQGSTVTVSS 61G5V_(H)56 398 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQSPGKGLEWVSVISGSGGDTYYADSVK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDHTSGWYYYGMDVWGQGTTVTVSS 56G3.2 V_(H)80 399QVQLQESGPGLVKPSETLSLTCTVSDGSISSYYW NWIRQPAGKGLEWIGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLNLTSVTAADTAVYYCARGP LWFDYWGQGTLVTVSS 48G4 V_(H)83 400QVQLVQSGAEVKKPGASVKVSCKVSGYTLTEL 53C3.1 SIHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYC ATHSGSGRFYYYYYGMDVWGQGTTVTVSS 61H5V_(H)86 401 QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSY 52B9YWGWIRQPPGKGLEWIGSIYYSGTTYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYCARVAAVYWYFDLWGRGTLVTVSS 50D4 V_(H)87 402 QVQLVQSGAEVKKTGASVKVSCKASGYTFTSHDINWVRQATGHGLEWMGWMNPYSGSTGLAQR FQDRVTMTRNTSISTAYMELSSLRSEDTAVYYCARDLSSGYYYYGLDVWGQGTTVTVSS 50G5v1 V_(H)88 403QVQLVQSGAEVKKPGASVKVSCKASGYPFIGY 50G5v2 YMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSITTAYMELSRLRSDDTAVFY CARGGYSYGYEDYYGMDVWGQGTTVTVSS 51C1V_(H)89 404 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS RVTISLDTSHDQFSLRLTSVTAADTAVYYCARVTGTDAFDFWGQGTMVTVSS 53C3.2 V_(H)90 405 QVQLQESGPGLVKPSQTLSLTCTVSNGSINSGNYYWSWIRQHPGKGLEWIGYIYHSGSAYYNPSL KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARTTGASDIWGQGIMVTVSS 54H10.3 V_(H)91 406DIQMTQSPSSLSASVGDRVTITCRASQTISIYLN WYQQKPGKAPKFLIYSASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFSTYFCQQSYSSPLTFGGGT KVEIKR 55A7 V_(H)92 407QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYW SWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLRLSSVTAADTAVYYCARGITGT IDFWGQGTLVTVSS 55E6 V_(H)93 408EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYS MNWVRQAPGKGLEWISYISSGSSTIYHADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAR EGYYDSSGYYYNGMDVWGQGTTVTVSS 61E1V_(H)94 409 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAV SVKSRITITPDTSKNQFSLQLKSVTPEDTAIYYCAREGSWSSFFDYWGQGTLVTVSS

TABLE 2C Coding Sequence for Antibody Variable Light (V_(L)) ChainsContained SEQ ID in Clone Designation NO. Coding Sequence 63E6 V_(L)6410 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGACAAGTCAGAGTATTAGCAGCTATTTAA ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAACCTCCTGATCTATGCTGCATCCAGTTTGCAAAG TGGGGTCCCATCAAGATTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGGTCTG CAACCTGAAGATTTTTCAACTTACTACTGTCAACAGAGTTACAGTACCTCGCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAACGA 66D4 V_(L)18411 GACATCCAGATGACCCAGTCGCCATCCTCCCTGT CTGCATCTGTAGGAGACAGGATCACCATCACTTGCCGGGCAAGTCAGATCATTAGCAGGTATTTAA ATTGGTATCAGCAGAACCCAGGGAAAGCCCCTAAGCTCCTGATCTCTGCTGCATCCAGTTTGCAAAG TGGAGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGCCAGATTTCACTCTCACCATCAGCAGTCTG CAACCTGAAGATTTTACAACTTACTACTGTCAACAGAGTTACAGTTCCCCGCTCACTTTCGGCGGAG GGACCAAGGTGGAGGTCAAACGA 66B4 V_(L)11412 GACATCCAGATGACCCAGTCTCCATCTTCCGTGT CTTCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGTATTAGCAGGTGGTTAG CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGAAAAG TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCT GCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGCTAACAGTTTCCCTCCGACGTTCGGCCAA GGGACCAAGGTGGAAATCAAACGA 65B1 V_(L)19413 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAACATTAACAACTATTTAA ATTGGTATCGGCAGAAACCAGGGAAAGCCCCTGAACTCCTGATCTATACTACATCCAGTTTGCAAAG TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG GAAACTGAAGATTTTGAAACTTACTACTGTCAACAGAGTTACAGTACCCCTCTCACTTTCGGCGGA GGGACCAAGGTGGAGATCAAACGA 65B4 V_(L)21414 TCCTATGTGCTGACTCAGCCACCCTCGGTGTCAG TGGCCCCAGGACAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCAGT GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCGTCTACGATGATAGCGACCGGCCCTCAG GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCTCCCTGACCATCAGCAGGGTCGA AGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTAGTAGTGATCATGTGGTATTCGG CGGAGGGACCAAGCTGACCGTCCTAGGT 67A4V_(L)20 415 TCCTATGTGCTGACTCAGCCACCCTCGGTGTCAGTGGCCCCAGGACAGACGGCCAGGATTACCTGTG GGGGAAACAACATTGGAAGTAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGC TGGTCGTCTATGATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG GAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGT GTGGGATAGTAGTAGTGATCATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 63A10v1 V_(L)22 416TCCTATGAGCTGACTCAGCCACACTCAGTGTCA GTGGCCACAGCACAGATGGCCAGGATCACCTGTGGGGGAAACAACATTGGAAGTAAAGCT GTGCACTGGTACCAGCAAAAGCCAGGCCAGGACCCTGTGCTGGTCATCTATTGCGATAGC AACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACCCAGGGAACACCGCCACC CTAACCATCAGCAGGATCGAGGCTGGGGATGAGGCTGACTATTACTGTCAGGTGTGGGAC AGTAGTAGTGATGGGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 63A10v2 V_(L)101 1857TCCTATGAGCTGACTCAGCCACACTCAGTGTCA GTGGCCACAGCACAGATGGCCAGGATCACCTGTGGGGGAAACAACATTGGAAGTAAAGCT GTGCACTGGTACCAGCAAAAGCCAGGCCAGGACCCTGTGCTGGTCATCTATTGCGATAGC AACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACCCAGGGAACACCGCCACC CTAACCATCAGCAGGATCGAGGCTGGGGATGAGGCTGACTATTACTGTCAGGCGTGGGAC AGCACCACTGTGGTATTCGGCGGAGGGACCAAGTTGACCGTCCTAGGT 63A10v3 V_(L)102 1858ACCTGCTCTGGAGATAAATTGGGGAATAGATAT ACTTGCTGGTATCAGCAGAAGTCAGGCCAGTCCCCTGTGCTGGTCATCTATCAAGATAGCG AGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTC TGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGTGGGAC AGCACCACTGTGGTATTCGGCGGAGGGACCAAGTTGACCGTCCTAGGT 65H11v1 V_(L)23 417TCCTATGAGCTGACTCAGCCACACTCAGTGTCA GTGGCCACAGCACAGATGGCCAGGATCACCTGTGGGGGAAACAACATTGGAAGTAAAACTGTGCAC TGGTTCCAGCAAAAGCCAGGCCAGGACCCTGTGCTGGTCATCTATAGCGATAGCAACCGGCCCTCA GGGATCCCTGAGCGATTCTCTGGCTCCAACCCAGGGAACACCGCCACCCTAACCATCAGCAGGATC GAGGCTGGGGATGAGGCTGACTATTACTGTCAGGTGTGGGACAGTAGTTGTGATGGGGTATTCGGC GGAGGGACCAAGCTGACCGTCCTAGGT 65H11v2V_(L)103 1859 TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAACATC ACCTGCTCTGGAGATAAATTGGGGGATAGATATGTTTGTTGGTATCAGCAGAAGCCAGGC CAGTCCCCTGTGCTGGTCATCTATCAAGATAGCAAGCGGCCCTCAGGGATCCCTGAACAA TTCTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATA GATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCATCACTGTGGTATTCGGCGGAGGG ACCAAGCTGACCGTCCTAGGT 67G10v1 V_(L)9 418TCCTATGAGCTGACTCAGCCACACTCAGTGTCA GTGGCCACAGCACAGATGGCCAGGATCACCTGTGGGGGAAACAACATTGGAAGTAAAGCTGTGCAC TGGTACCAGCAAAAGCCAGGCCAGGACCCTGTGCTGGTCATCTATAGCGATAGCAACCGGCCCTCA GGGATCCCTGAGCGATTCTCTGGCTCCAACCCAGGGAACACCGCCACCCTAACCATCAGCAGGATC GAGGCTGGGGATGAGGCTGACTATTACTGTCAGGTGTGGGACAGTAGTAGTGATGGGGTATTCGGC GGAGGGACCAAGCTGACCGTCCTAGGT 67G10v2V_(L)10 419 TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGCT CTGGAGATAAATTGGGGGATAAATATGCTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTGTGC TGGTCATCTATCAAGATAACGAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG GAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGC GTGGGACAGCACCACTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 64C8 V_(L)24 420GATGTTGTGATGACTCAGTCTCCGCTCTCCCTGC CCGTCACCCTTGGACAGCCGGCCTCCATCTCCCGCAGGTCTAGTCCAAGCCTCGTATACAGTGATGG AAACACCTACTTGAATTGCTTTCAGCAGAGGCCAGGCCACTCTCCAAGGCGCCTAATTTATAAGGG TTCTAACTGGGACTCAGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACTCT GAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGTATTTATTACTGCATACAAGATACACACTGGCCC ACGTGCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA 64A8 V_(L)1 421 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT 67B4CTGCATCTGTAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA AGCGCCTGATCTATGCTGCATCCAATTTGCAAAGGGGGGTCCCATCAAGGTTCAGCGGCAGTGGAT CTGGGACAGAATTCACTCTCACAATCAGCACCCTGCAGCCTGAAGATTTTGCAACTTATTCCTGTCT CCAGCATAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 63G8v1 V_(L)104 1860GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGACATTAGAAAT GATTTAGGCTGGTATCAACAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA TCCAATTTGCAAAGGGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTC ACTCTCACAATCAGCACCCTGCAGCCTGACGATTTTGCAACTTATTCCTGTCTCCAGCATA ATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 63G8v2 V_(L)105 1861GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGAAGT GGTTTAGGCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA TCCAATTTGCAAAGGGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTC ACTCTCACAGTCAGCAGTCTGCAGCCTGAAGATTTTGCAACTTATTCCTGTCTCCAGCATA ATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 63G8v3 V_(L)106 1862GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGAAGT GGTTTAGGCTGGTATCAACAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA TCCAATTTGCAAAGGGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTC ACTCTCACAGTCAGCAGTCTGCAGCCTGAAGATTTTGCAACTTATTCCTGTCTCCAACATA ATACTTACCCTCTCACTTTCGGCGGAGGGACCAAGGGGGAGATCAGACGA 66G2 V_(L)12 422GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGAAATGATTTAG GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCAATTTGCAAA GTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAAAATTCACTCTCACAATCAACAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAACTTAATGGTTACCCTCTCACTTTCGGCGGA GGGACCAAGGTGGAGATCAAACGA 68D3v1V_(L)2 423 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT 68D3v2CTGCATCTGTAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAACAGAAACCAGGGAAAGCCCCTA AGCGCCTGATCTATGCTGCATCCAATTTGCAAAGGGGGGTCCCATCAAGGTTCAGCGGCAGTGGAT CTGGGACAGAATTCACTCTCACAATCAGCACCCTGCAGCCTGACGATTTTGCAACTTATTCCTGTCT CCAGCATAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 65D1 V_(L)27 424TCCTATGACCTGACTCAGCCACCCTCAGTGTCCG TGTCCCCAGGACAGACAGCCAGCATCACCTGCTCTGGAGATAAATTGGGGGATAAATATGTTTGCT GGTATCAGCAGAAGCCAGGCCAGTCCCCTGTGCTGGTCATCTATCAAGATAGTAAGCGGCCCTCAG GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGCGGGATCCA GGCTATGGATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCAGGGTATTCGGCGGAGGGACCA AGCTGACCGTCCTAGGT 65G4 V_(L)8 425TCCTATGAGATGACTCAGCCACTCTCAGTGTCAG 64H5TGGCCCTGGGACAGACGGCCAGGATTACCTGTG GGGGAAACAACATTGGAAGTAAAAATGTACACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGT TGGTCATCTATAGGGATAGCAAGCGGCCCTCTGGGATCCCTGAGCGATTCTCTGGCTCCAACTCGG GGAACACGGCCACCCTGACCATCAGCAGAGCCCAAGCCGGGGATGAGGCTGACTATTACTGTCAGG TGTGGGACAGCAGTAGTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 65D4 V_(L)26 426TCCTATGAGCTGACTCAGCCACTCTCAGTGTCTG TGGCCCTGGGCCAGACGGCCAGGATTCCCTGTGGGGGAAATGACATTGGAAGTAAAAATGTGCACT GGTACCAGCAGAAACCAGGCCAGGCCCCTGTGCTGGTCATCTATAGGGATCGCAACCGGCCCTCTG GGATCCCTGAGCGATTCTCTGGCTCCAACTCGGGGAACACGGCCACCCTGACCATCAGCAGAGCCC AAGCCGGGGATGAGGCTGACTATTACTGTCAGGTGTGGGACAGCAACCCTGTGGTATTCGGCGGAG GGACCAAGCTGACCGTCCTAGGT 65E3 V_(L)25427 TCCTATGAGCTGACTCAGCCACTCTCAGTGTCAG TGGCCCTGGGACAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAATGTGCACT GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATAGGGATAGAAACCGGCCCTCTG GGATCCCTGAGCGATTCTCTGGCTCCAACTCGGGGAACACGGCCACCCTGACCATCAGCAGAGCCC AAGCCGGGGATGAGGCTGACTATTACTGTCAGGTGTGGGACAGCAGCACTGTGGTCTTCGGCGGAG GGACCAAGCTGACCGTCCTAGGT 68G5 V_(L)13428 TCCTATGAGCTGACTCAGCCACTCTCAGTGTCAG TGGCCCTGGGACAGACGGCCAGGCTTACCTGTGGGGGTAACAACATTGGAAGTATAAATGTGCACT GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGTTGGTCATCTATAGGGATAGGAACCGGCCCTCTG GGATCCCTGAGCGATTCTCTGGCTCCAACTCGGGTAACACGGCCACCCTGACCATCAGCAGAGCCC AAGCCGGGGATGAGGCTGACTATTACTGTCAGTTGTGGGACAGCAGCACTGTGGTTTTCGGCGGAG GGACCAAGCTGACCGTCCTAGGT 67G8 V_(L)28429 TCCTATGAGCTGACTCAGCCACTCTCAGTGTCAG TGGCCCTGGGACAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTTACAATGTGTTCT GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATAGGGATAGCAAGCGGCCCTCTG GGATCCCTGAGCGATTCTCTGGCTCCAACTCGGGGAACACGGCCACCCTGACCATCAGCAGAGCCC AAGCCGGGGATGAGGCTGACTATCACTGTCAGGTGTGGGACAGCAGCACTGTGGTATTCGGCGGAG GGACCAAGCTGACCGTCCTAGGT 65B7v1 V_(L)29430 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGC ATCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTG CATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGT ATGGTAGCTCGTGCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA 65B7v2 V_(L)107 1863GATGTTGTGATGACTCAGTCTCCACTCTCCCTGC CCGTCACCCTTGGACAGCCGGCCTCCATCTCCTACAGGTCTAGTCAAAGCCTCGTATACA GTGATGGAGACACCTACTTGAATTGGTTTCAGCAGAGGCCAGGCCAATCTCCAAGGCGC CTAATTTATAAGGTTTCTAACTGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGG TCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGGGTTTAT TACTGCATGCAAGGTACACACTGGCGGGGTTGGACGTTCGGCCAAGGGACCAAGGTGGAA ATCAAACGA 63B6 V_(L)4 431GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG 64D4TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT GCAGGGCCAGTCAGAGTGTTAGTAACAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTC CCAGGCTCCTCATCTATGGTGCATTCAGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGG GTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTATATTACTGT CAGCAGTTTGGTAGGTCATTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAGACGA 63F5 V_(L)14 432GAAGTTGTGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGACTGTTAGGAACAACTACT TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTCCCAGGCTCCTCATCTTTGGTGCGTCCAGCAGGGC CACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAG ACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTTTGGTAGTTCACTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAACGA 65E8 V_(L)3433 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG 63H11TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT 64E6GCAGGGCCAGTCAGAGTGTTAGGAACAGCTACT 65F11TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTC 67G7CCAGGCTCCTCATCTATGGTGCATTTAGCAGGGC CTCTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAG ACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTTTGGAAGCTCACTCACTTTCGGCGGA GGGACCAAGGTGGAGATCAAACGA 65C1 V_(L)16434 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGACTATTAGGAACAGCTACT TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGG CCACTGGCATCCCAGACAGGTTCAGTGGCGGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTTTGGTAGCTCACTCACTTTCGGCGG AGGGACCAAGGTGGAGATCAAACGA 66F6V_(L)15 435 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT GCAGGGCCAGTCAGAGTGTTAGGAACAGCTACTTAGCCTGGTACCAGCAGCAACCTGGCCAGGCTC CCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTG GGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACT GTCAGCAGTTTGGTAGCTCACTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 64A6 V_(L)30 436GAAATACTGATGACGCAGTCTCCAGCCACCCTG TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAACAGCAACTTAG CCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTACATCCACCAGGGCCA CTGGTGTCCCAGCCAGGTTCGGTGGCAGTGGGTCTGGGACAGAATTCACTCTCACCATCAGCAGCC TGCAGTCTGAAGATTTTGCATTTTATTACTGTCAGCAATATAATACCTGGCCGTGGACGTTCGGCCA AGGGACCAAGGTGGAAATCAAACGA 65F9 V_(L)31437 GAAATACTGATGACGCAGTCTCCAGCCACCCTG TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAG CCTGGTACCAGCAGAAACCTGGCCAGTCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCA CTGGTATCCCAGCCAGGTTCGGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCC TGCAGTCTGAAGATTTTGCATTTTATTACTGTCAGCAGTATAATACCTGGCCGTGGACGTTCGGCCA AGGGACCAAGGTGGAAATCAAACGA 64A7 V_(L)17438 GAAATTGTATTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGTCGCAACTACT TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGG CCACTGGCGTCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGTTCATCTCTGTGCAGTTT TGGCCAGGGGACCAACCTGGACATCAGACGA 65C3V_(L)5 439 GAAATGGTGATGACGCAGTCCCCAGCCACCCTG 68D5TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCT GCAGGGCCAGTCAGAGTGTTAGCAGCCAGTTAGCCTGGTACCAGGAGAAACCTGGCCGGGCTCCCA GGCTCCTCATCTATGGTGCCTCCAACAGGGCCATTGATATCCCAGCCAGGTTAAGTGGCAGTGGGTC TGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCTGTTTATTACTGTCAG CAGTATAATAACTGGCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAATTCAAACGA 67F5 V_(L)32 440GAAATAGTGATGACGCAGTCTCCAGCCACCCTG TCTGTGTCTCCAGGGGAAAGAGTCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAG CCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATACATGGTTCATCCAACAGGGCCA TTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCC TGCAGTCTGCAGATTTTGCTGTTTATAACTGTCAGCAGTATGAAATTTGGCCGTGGACGTTCGGCCA AGGGACCAAGGTGGAAATCAAACGA 64B10v1V_(L)33 441 CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG 64B10v2CGGCCCCAGGACAGAAGGTCACCATCTCCTGCT CTGGAAGCAGCTCCAATATTGGGAATAATTATGTAGCCTGGTACCAGCAGCTCCCAGGAACAGCCC CCAAACTCCTCATTTATGACAATGATAAGCGACCCTCAGGGATTCCTGACCGATTCTCTGGCTCCAA GTCTGGCACGTCAGCCACCCTGGGCATCACCGGACTCCAGACTGGGGACGAGGCCGATTATTACTG CGGAACATGGGATAGCAGCCTGAGTGCTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 68C8 V_(L)34 442CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG CGGCCCCAGGACAGAAGGTCACCATCTCCTGCTCTGGAAGCAGTTCCAACATTGGAAATAATTATG TATCCTGGTACCAGCAGCTCCCAGGAACAGCCCCCAAACTCCTCATTTATGACAATAATAAGCGAC CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACGTCAGCCACCCTGGGCATCACCGG ACTCCAGACTGGGGACGAGGCCGATTATTACTGCGGAACATGGGATAGCAGCCTGAGTGCTGTGGT ATTCGGCGGAGGGACCAAACTGACCGTCCTAGGT67A5 V_(L)35 443 GATATTGTGATGACCCAGACTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCTTAAATAGTGATGATGGAAATACCTATTTGGACTGGTACCTGCAGAA GCCAGGGCAGTCTCCACAACTCCTGATCTATACGCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG GTTCAGTGGCACTGGGTCAGGCACTGAATTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT TGGAGTTTATTACTGCATGCAACGTCTAGAGTTTCCTATTACCTTCGGCCAAGGGACACGACTGGAG ATTAAACGA 67C10 V_(L)36 444GATTTTGTGATGACCCAGACTCCACTCTCCCTGC CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTCTTAAATAGTGATGA TGGAAACACCTATTTGGACTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATAC GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAGGTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGAGTTTATTACTGCATGCAACGTATAGAGTTT CCTATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACGA 64H6 V_(L)37 445 TCCTACGAGCTGACTCAGCCACTCTCAGTGTCAGTGGCCCTGGGACAGACGGCCAGGATTACCTGTG GGGGAAACAACATTGGAAGTAAAAATGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGG TGGTCATCTATAGGGATAGCAAGCGGCCCTCTGGGATCCCTGAGCGATTCTCTGGCTCCAACTCGG GGAACACGGCCACCCTGACCATCAGCAGAGCCCAAGCCGGGGATGAGGCTGACTATTACTGTCAGG TGTGGGACAGCAGTCCTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 63F9 V_(L)38 446GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGTATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAG CCTGGTATCAGCAGACACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTTCATCCAGTTTGCAAAG TGGGGTCCCATCAAGGTTCAGCGGCACTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCT GCAGCCTGAAGATTTTGCAACTTATTTCTGTCTACAGCGTAATAGTTACCCGCTCACTTTCGGCGGA GGGACCAAGGTGGAGATCAAACGA 67F6v1V_(L)39 447 GATATTGTAATGACCCAGACCCCACTCTCCCTGCCCGTCATCCCTGGAGAGCCGGCCTCCATCTTCTG CAGGTCTAGTCAGAGCCTCTTAAATAGTGATGCTGGTACCACCTATTTGGACTGGTACCTGCAGAA GCCAGGGCAGTCTCCACAACTCCTGATCTATACGCTTTCCTTTCGGGCCTCTGGAGTCCCAGACAGG TTCAGTGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCACTAGGGTGGAGGCTGAGGATGTT GGAGTTTATTATTGCATGCAACGTATAGAGTTCCCTATCACCTTCGGCCAAGGGACACGACTGGAGA TTAAACGA 67F6v2 V_(L)108 1864GATATTGTAATGACCCAGACCCCACTCTCCCTGC CCGTCATCCCTGGAGAGCCGGCCTCCATCTTCTGCAGGTCTAGTCAGAGCCTCTTAAATAGTGATGC TGGTACCACCTATTTGGACTGGTACCTGCAGAAGCCAGGGCGGTCTCCACAACTCCTGATCTATAC GCTTTCCTTTCGGGCCTCTGGAGTCCCAGACAGGTTCAGTGGCAGTGGGTCAGGCACTGATTTCACA CTGAAAATCACTAGGGTGGAGGCTGAGGATGTTGGAGTTTATTATTGCATGCAACGTATAGAGTTCC CTATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACGA 48C9 V_(L)78 448 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT 49A12CTGCATCTATAGGAGACAGAGTCACCATCACTT 51E2 GCCGGGCAAGTCAGAACATTAGGACCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA AGCTCCTGATTTATGTTGCATCCAGTTTGGAAAGTGGGGTCCCATCAAGGTTCAGTGGCACTGGATC TGGGACAGATTTCGCTCTCACCATCAGCAGTCTCCAACCTGAAGATTTTGCAACTTACTACTGTCAAC AGAGTGACAGTATCCCTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGA 48F3 V_(L)77 449GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGGATTAGCAGTTATTTAA ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGTTCTTGATATATGCTGTATCCAGTTTGCAAAG TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG GAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTGCTACATTCACTTTCGGCCCTGG GACCAAAGTGGATATCAAACGA 48F8 V_(L)49450 GAAATTGTGCTGACTCAGTCTCCAGACTTTCAGT 53B9CTGTGACTCCAAAGGAGAAAGTCACCATCACCT 56B4 GCCGGGCCAGTCAGGACATTGGTAATAGCTTAC57E7 ACTGGTACCAGCAGAAACCAGATCAGTCTCCAA 57F11AGCTCCTCATCAAGTTTGCTTCCCAGTCCTTCTC AGGGGTCCCCTCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCGCCCTCACCATCAATAGCCT GGAAGCTGAAGATGCTGCAACGTATTACTGTCATCAGAGTAGTGATTTACCGCTCACTTTCGGCGGA GGGACCAAGGTGGACATCAAACGA 48H11V_(L)40 451 GACATCCAGATGACCCAGTCTCCATCCTCTCTGTCTACATCTGTAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGAACATTAGGAGCTATTTAAATTGGTATCAACTGAAACCAGGGAAAGCCCCTA AGGTCCTGATCTATGGTGCATCTAATTTACAGAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC TGGGACAGATTTCACTCTCACCATCAGCAATCTGCAATCTGAAGATTTTGCAATTTACTACTGTCAAC AGAGTTACAATACCCCGTGCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA 49A10 V_(L)65 452GATATTGTGATGACCCAGACTCCACTCTCCCTGC 48D4CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCTTGGATAGTGATGATGGAAACACCTATTTGGACTGGTACCTGCAGAA GCCAGGGCAGTCTCCACAGCTCCTGATCTATACGCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG GTTCAGTGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT TGGAGTTTATTACTGCATGCAACGTATAGAGTTTCCGATCACCTTCGGCCAAGGGACACGACTGGAG ATTAAACGA 49C8 V_(L)45 453GACATCCAGATGACCCAGTCTCCATCCTCCCTGT 52H1CTGCATCTGTAGGAGACAGAGTCACCTTCACTT GCCAGGCGAGTCAGGACATTAACATCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA AGCTCCTGATCTACGATGTATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATC TGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAAC AATATGATAATCTCCCATTCACTTTCGGCCCTGGGACCAAAGTGGATCTCAAACGA 49G2 V_(L)66 454GATATTGTGTTGACCCAGACTCCACTCTCCCTGC 50C12CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG 55G11CAGGTCTAGTCAGAGCCTCTTGGATAGTGATGA TGGAGACACCTATTTGGACTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATAC GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAGGTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGAGTTTATTACTGCATGCAACATATAGAATTT CCTTCGACCTTCGGCCAAGGGACACGACTGGAGATTAAACGA 49G3 V_(L)47 455 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTATAGGAGACAGAGTCACCATCACTT GCCAGGCGAGTCAGGGCATTAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA AGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGAT CTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCTACATATTACTGTCAC CAGTATGATGATCTCCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAGACGA 49H12 V_(L)43 456GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAAGACATTACCAAATATTTAA ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATACATTCATTTTGGAAAC AGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTG CAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGACAATTTACCGCTCACCTTCGGCCAA GGGACACGACTGGAGATTAAACGA 51A8 V_(L)61457 AATTTTATACTGACTCAGCCCCACTCTGTGTCGG AGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCCGCAGCAGTGGCAGCATTGCCAGCGACTATG TGCAGTGGTACCAGCAGCGCCCGGGCAGTTCCCCCACCACTGTGATCTATGAGGATAAAGAAAGAT CCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGTTCCTCCAACTCTGCCTCCCTCACCATC TCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATCGCAACAATCATGTGG TTTTCGGCGGAGGGACCAAGCTGACCGTCCTAG GT51C10.1 V_(L)55 458 TCCTATGAGTTGACACAGCCGCCCTCGGTGTCTGTGTCCCCAGGCCAAACGGCCAGGATCACCTGCT CTGGAGATGCATTGCCAAAAAAATATGCTTATTGGTACCAGCAGAAGTCAGGCCAGGCCCCTGTGC TGGTCATCTATGAGGACAGCAAACGACCCTCCGGGATCCCTGAGAGATTCTCTGGCTCCATCTCAGG GACAATGGCCACCTTGACTATCAGTGGGGCCCAGGTGGAGGATGAAGCTGACTACTACTGTTACTC AACAGACAGCAGTGTTAATCATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 51C10.2 V_(L)70 459TCCTATGACCTGACTCAGCCACCCTCAGTGTCCG TGTCCCCAGGACAGACAGCCAGCATCACCTGCTCTGGAGACGAATTGGGGGATAAATATGCTTGCT GGTATCAGCAGAAGCCAGGCCAGTCCCCTGTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAG GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGCGGGACCCA GGCTATGGATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCGGCACTGTGGTATTCGGCGGAGG GACCAAACTGACCGTCCTAGGT 51E5 V_(L)79460 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAG GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAACCGCCTGATCTATGCTGCATCCAGTTTGCAATT TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCT GCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAACATAGTAGTTACCCGCTCACTTTCGGCGGA GGGACCAGGGTGGAGATCAAACGA 51G2 V_(L)51461 GACATCCAGATGACCCAGTCTCCATCTTCCGTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGTATTAGCAGCTGGTTAG CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGATGCATCCAGTTTGCAAAG TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCT GCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGACTAACAGTTTCCCTCCGTGGACGTTCGGCC AAGGGACCAAGGTGGAAATCAAACGA 52A8V_(L)41 462 GACATCCAGATGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGACTATTAGCAGTTATTTAAATTGGCATCAGCAGAAACCAGGGAAAGCCCCTA AGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC TGGGACAGATTTCAGTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAG CAGAGTTACAGTACCCCGCTCACTTTCGGCGGCGGGACCAAGGTGGAGATCAAACGA 52B8 V_(L)82 463GAAGTTGTGCTGACGCAGTCTCCAGCCACCCTG TCTGTGTCTCCAGGGGGAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCGACATCTTAG CCTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCA CTGGTATCCCAGCCAGGTTCAGTGGCGGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGTAGCC TGCAGTCTGAAGATTTTGCAGTTTATTTCTGTCAGCAGTATAATAACTGGCCGCTCACTTTCGGCGG AGGGACCAAGGTGGAGATCAAACGA 52C1 V_(L)67464 CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG CGGCCCCAGGACAGAAGGTCACCATCTCCTGCTCTGGAAGCAGCTCCAACATTGGGATTAATTATG TATCCTGGTACCAGCAGCTCCCAGGAACAGCCCCCAAACTCCTCATTTATGACAATAATAAGCGAC CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACGTCAGCCACCCTGGGCATCACCGG ACTCCAGACTGGGGACGAGGCCGATTATTGCTGCGGAACATGGGATAGCAGCCTGAGTGCTGTGGT ATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT52F8 V_(L)42 465 GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACCTGCAGAAGCC AGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTC AGTGGCAGGGGGTCAGGCACAGATTTTTCACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGG ATTTATTACTGCATGCAAGCTCTACAAACTCCATTCACTTTCGGCCCTGGGACCAATGTGGATATCA AACAA 52H2 V_(L)84 466GAAAATGTGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCTTGTAGGGCCAGTCAGAGTGTTAGAAGCAGCTACT TAGCCTGGTACCAGCAGAGACCTGGCCAGGCTCCCAGGCTCCTCATCTTTGGTGCATCCAGGAGGG CCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGTTCACCTCGCAGTTTTGG CCAGGGGACCAAGCTGGAGATCAAACGA 53F6V_(L)63 467 GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCCAGCATAGTAATGGATACAACTATTTGGATTGGTACCTGCAGAAGCC AGGACAGTCTCCACAGTTATTGATCTATTTGGATTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTC AGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATATTGGG GTTTATTACTGCATGCAAGGTCTACAAACTCCTCCCACTTTCGGCGGAGGGACCAAGGTGGAGATCA AACGA 53H5.2 V_(L)62 468GACATCCAGATGACCCAGTCTCCATCTTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGAAATGATTTAG GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCAAA GTGGGGTCCCATCAAGGTTCAGCGGCAGCGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAAGAGTTACCCATTCACTTTCGGCCCT GGGACCAAAATGGATATCAAAGGA 53H5.3V_(L)80 469 GAAATAGTGATGACGCAGTCTCCAGTCACCTTGTCTGTGTCTCCAGGGGAAAGAGCCATCATCTCCT GCAGGGCCAGTCAGAGTGTTAGCAGCAACGTCGCCTGGTACCAGCAGAAACCTGGCCAGACTCCCA GGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTCTCCCAACCAGGTTTAGTGGCAGTGGGT CTGGGACAGTGTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAGTTTATTACTGTCAG CAGTTTAGTAACTCAATCACCTTCGGCCAAGGGACACGACTGGAGATTAAACGA 54A1 V_(L)44 470GACATCCAGATGGCCCAGTCTCCATCCTCCCTGT 55G9CTGCATCTGTTGGAGACAGAGTCACCATCACTT GCCAGGCGAGTCAGGACATTAGCATCTATTTAAATTGGTATCAGCTGAAACCAGGGAAAGCCCCTA AGCTCCTGATCTACGATGTATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAGGTGGATC TGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAA CAGTATGATAATCTCCCTCTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGA 54H10.1 V_(L)53 471GAAATTGTGGTGACGCAGTCTCCAGGCACCCTG 55D1TCTTTGTCTGTAGGGGAAAGAGCCATCCTCTCCT 48H3GCAGGGCCAGTCAGAGTTTTAGCAGCAGTTACT 53C11TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTC CCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGCGGCAGTG GGTCTGGGACAGACTTCACTCTCACCATCAGTAGACTGGAGCCTGAAGATTTTGCAGTGTATTACT GTCAGCAGTATGGTAGCTCACGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGA 55D3 V_(L)71 472GACATCCAGATGACCCAGTCTCCATCCTCACTGT CTGTATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGACATTAGCAATTATTTAG CCTGGTTTCAGCAGAAACCAGGGAAAGCCCCTAAGTCCCTGATCTATGCTGCATCCAGTTTGCAAAG TGGGGTCCCATCAAAGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCT GCAGCCTGAAGATTTTGCAACTTATTACTGCCAACAGTATAATATTTACCCTCGGACGTTCGGCCAA GGGACCAAGGTGGAAATCAAGCGA 55E4 V_(L)75473 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT 49B11CTACATCTATAGGAGACAGAATCACCATCACTT 50H10GCCGGGCAAGTCAGAGCATTAGTAACTATTTAA 53C1 ATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTAGGCTCCTGATCTATACAGCTTCCAGTTTGCAAAG TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG CAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTCCAGTATCCCTTGGACGTTCGGCCAAG GGACCAAGGTGGAAATCAAACGA 55E9 V_(L)68474 GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCCTGCATAGTAACGGATTCAACTATTTGGATTGGTACCTGCAGAAGCC AGGGCAGTCTCCACAGGTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTC AGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGG ATTTATTACTGCATGCAAGCTCTACAAACTCTCATCACCTTCGGCCAAGGGACACGACTGGAGATTA AACGA 55G5 V_(L)83 475TCCTATGAACTGACTCAGCCACCCTCAGTGTCCG TGTCCCCAGGACAGACAGCCAGCATCACCTGCTCTGGAGATAATTTGGGGGATAAATATGCTTTCT GGTATCAACAGAAGCCAGGCCAGTCCCCTGTATTGGTCATCTATCAAGATAACAAGCGGCCCTCAG GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGCGGGACCCA GGCTGTGGATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCGCCACTGTGATTTTCGGCGGAGG GACCAAGTTGACCGTCCTAGGT 56A7 V_(L)52476 GACATCCAAATGACCCAGTCTCCATCTTCCGTGT 56E4CTGCATCTGTAGGAGACAGAGTCACCATCACTT GTCGGGCGAGTCAGGATATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA AATTCCTGATCTATGATGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC TGGGGCAGATTTCACTCTCACCATCAACAACCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAA CAGACTAACAGTTTTCCTCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGA 56C11 V_(L)64 477TCCTATGTGCTGACTCAGCCACCCTCGGTGTCAG TGGCCCCAGGACAGGCGGCCAGGATTACCTGTGGGGGAAACGACATTGGAAGTAAAAGTGTGCACT GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCGTCTATGATGATAGCGACCGGCCCTCAG GGATCCCTGAGCGATTCTCTGGCTCCAAGTCTGGGAACACGGCCACCCTGATTATCAGCAGGGTCGA AGCCGGGGAAGAGGCCGACTATTATTGTCAGGTGTGGGATAGTAGTAGTGATGTGGTATTCGGCGG AGGGACCAAGTTGACCGTCCTAGGT 56E7 V_(L)86478 GACCTCCAGATGACCCAGTCTCCTTCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAAAAAATTTTTAA ATTGGTATCAGCAGAAACCAGGTAAAGCCCCTAACCTCCTGATCTACGATGCATCCAATTTGGAAAC AGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTG CAGCCTGAAGATATTGCAACATATTACTGTCAACAATATGCTATTCTCCCATTCACTTTCGGCCCTG GGACCACAGTGGATATCAAACGA 56G1 V_(L)76479 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAACTATTTAA ATTGGTTTCTGCAGATACCAGGGAAAGCCCCTAAACTCCTGATCTATGCAGCTTCCAGTTTACAAAG TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAACAGTCTG CAACCTGAAGATTTTGGAACTTACTACTGCCAACAGAGTTCCACTATCCCTTGGACGTTCGGCCAA GGGACCAAGGTGGAAATCAAACGA 56G3.3V_(L)81 480 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG 55B10TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT GCAGGGCCAGTCAGAGTGTTAGCAGAGACTACTTAGCCTGGTATCGGCAGAAACCTGGCCAGGCTC CCAGGCTCCTCGTCTATGGTGCATCCGCCAGGGCCACTGGCATCCCAGACAGATTCAGTGGCAGTG GGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACT GTCAGCAATATGGTAGATCACTATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGA 57B12 V_(L)72 481GACATCCAGATGACCCAGTCTCCATCCTCACTGT CTGTATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCATGACATTAGCAATTATTTAG CCTGGTTTCAGCAGAAACCAGGGAAAGCCCCTAAGTCCCTGATCTATGCTGCATCCAGTTTGCAAAG TGGGGTCCCATCAAAGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCT GCAGCCTGAAGATTTTGCAACTTATTACTGCCAACAATATAATACTTACCCTCGGACGTTCGGCCAA GGGACCAAGGTGGAAATCAAGCGA 57D9 V_(L)87482 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCCGAGTGTTAGCAGCAGCTACT TAGCCTGGTACCAGCAGAAACCTGCCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGTAGGG CCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCATCAGTATGGTACCTCACCGTGCAGTTTTGG CCAGGGGACCAAGCTGGAGATCAAACGA 59A10V_(L)48 483 GACATCCAGATGACCCAGTCTCCATCTTCCGTGT 49H4CTGCATCTGTAGGAGACAGAGTCACCATCACTT GTCGGGCGAGTCAGGGTATTAGCAGCTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA AACTCCTGATCTATGGTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC TGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTATTGTCAA CAGACTAACAGTTTCCCTCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGA 59C9 V_(L)50 484GACATCCAGATGACCCAGTCTCCATCTTCCGTGT 58A5CTGCATCTGTAGGAGACAGAGTCACCATCACTT 57A4 GTCGGGCGAGTCAGGATATTGACAGCTGGTTAG57F9 TCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAACCTCCTGATCTATGCTGCATCCAATTTGCAAAG AGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCGCCAGCCTG CAGCCTGAAGATTTTGCAACTTACTATTGTCAGCAGACTAACAGTTTCCCTCCGTGGACGTTCGGCC AAGGGACCAAGGTGGAAATCAAACGA 59G10.2V_(L)60 485 TCCTATGAGCTGTCTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGTCAGCATCACCTGCT CTGGAGATAATTTGGGGGATAAATATGCTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTGTCC TGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAATTCTGG GAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGC GTGGGACAGCAGCACTACATGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 59G10.3 V_(L)54 486CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG CGGCCCCAGGACAGAAGGTCACCATCTCCTGCTCTGGAAGCAGCTCCAACATTGGGGATAATTATG TATCCTGGTACCAGCAGTTCCCAGGAACAGCCCCCAAACTCCTCATTTATGACAATAATAAGCGAC CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACGTCAGCCACCCTGGGCATCACCGG ACTCCAGACTGGGGACGAGGCCGATTATTACTGCGGAACATGGGACAGCAGCCTGAGTGTTATGGT TTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT60D7 V_(L)69 487 GATATTGTGCTGACCCAGACTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCTTGGATAGTGATGATGGAGACACCTATTTGGACTGGTACCTGCAGAA GCCAGGGCAGTCTCCACAGCTCCTGATCTATACGCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG GTTCAGTGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT TGGAGTTTATTACTGCATGCAACGTATAGAGTTTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAG ATCAAACGA 60F9 V_(L)58 488GAAATTATGTTGACGCAGTCTCCAGGCACCCTG 48B4TCTTTGTCTCCAGGGGAAAGGGCCACCCTCTCCT 52D6GCAGGGCCAGTCAGAGGGTTCCCAGCAGCTACA TAGTCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTTCATCCAACAGGGC CACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCGGCAG ACTGGAGCCTGAAGATTTTGCAGTGTACTACTGTCAGCAGTATGGTAGCTCACCTCCGTGGACGTTC GGCCAAGGGACCAAGGTGGCAATCAAACGA 60G5.2V_(L)46 489 TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGCT CTGGAAATAAATTGGGGGATAAATATGTTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTGTCT TGGTCATCTATCAAGATAGCAAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG GAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTTTGGATGAGGCTGACTATTACTGTCAGGC GTGGGACAGCAGCACTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 61G5 V_(L)59 490GAAATTATGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGAGTTCCCAGCAGCTACT TAGTCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAACAGGG CCACAGGCATCCCAGACAGGTTCAGCGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCGGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGTTCACCTCCGTGGACGTT CGGCCAAGGGACCAAGGTGGCAATCAAACGA 52C5V_(L)73 491 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTATAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGAGCATTAGCAACTATTTAAATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTA GGCTCCTGATCTATGCAGCTTCCAGTTTGCAAAGTGGGGTCCCATCGAGGTTCAGTGGCAGTGGATC TGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAATTTACTACTGTCAAC AGAGTTCCAGTATCCCTTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGA 61H5 V_(L)88 492GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG 52B9TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT GCAGGGCCAGTCAGAGTGTTAGCAGAGACTACTTAGCCTGGTACCGGCAGAAACCTGGCCAGGCTC CCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGATTCAGTGGCAGTG GGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACT GTCAGCAATATGGTAGATCACTATTCACTTTCGGCCCTGGGACCACAGTGGATATCAAACGA 59D10v1 V_(L)56 493TCCTATGAGCTGACACAGCCACCCTCGGTGTCTG TGTCCCCAGGCCAAACGGCCAGGATCACCTGCTCTGGAGATGCAGTGCCAAAAAAATATGCTAATT GGTACCAGCAGAAGTCAGGCCAGGCCCCTGTGCTGGTCATCTATGAGGACAGCAAACGACCCTCCG GGATCCCTGAGAGATTCTCTGGCTCCAGCTCAGGGACAATGGCCACCTTGACTATCAGTGGGGCCC AGGTGGAGGATGAAGCTGACTACTACTGTTACTCAACAGACAGCAGTGGTAATCATGTGGTATTCG GCGGAGGGACCAAGCTGACCGTCCTAGGT 59D10v2V_(L)57 494 TCCTATGAGTTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGCT CTGGAGATAAATTGGGGGATAAATACGTTTGCTGGTATCAGCAGATGCCAGGCCAGTCCCCTGTGT TGGTCATCCATCAAAATAACAAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG GAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTATTGTCAGGC GTGGGATAGTAGTACTGCGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 56G3.2 V_(L)85 495GAAACAGTGATGACGCAGTCTCCAGCCACCCTG TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGGCAGAGTGTTGGCAGTAACTTAA TCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGACA CTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCC TGCAGTCTGAAGATTTTGCAGTTTATTACTGTCAGCAGTATAATAATTGGCCTCTCACTTTCGGCGGA GGGACCAAGGTGGAGATCAAACGA 66F7 V_(L)7496 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGACAAGTCAGAGCATTAGCAACTATTTAA ATTGGTATCAGCAGAAACCAGGAAAAGCCCCTAACCTCCTGATCTATGCTGCATCCAGTTTGCAAAG TGGGGTCCCATCAAGATTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGGTCTG CAACCTGAGGATTTTTCAACTTACTACTGTCAACAGAGTTACAGTACCTCGCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAACGA 48G4 V_(L)89497 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG 53C3.1TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT GCAGGGCCAGTCAGAGTGTTGCCAGCAGTTACTTAGTCTGGTACCAACAGAAACCTGGCCAGGCTC CCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTG GGTCTGGGACAGACTTCACTCTCACCATCAGGAGACTGGAGCCTGAAGATTTTGCAGTGTATTACT GTCAGCAGTATGGTACCTCACCATTTACTTTCGGCCCTGGGACCAAAGTGGATCTCAAACGA 50G1 V_(L)90 498GACATTGTGATGACCCAGACTCCACTCTCCCTGC CCGTCAGCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTCTTGGATAGTGATG ATGGAGACACCTATTTGGACTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATA CGCTTTCCTATCGGGCCTCTGGAGTCCCAGACAGGTTCAGTGTCAGTGGGTCAGGCACTGATTTCAC ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGAGTTTATTACTGCATGCAACGTATAGAGTTT CCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 58C2 V_(L)91 499 GAAATTGTGATGACCCAGACTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG CAGGTCTAGTCAGAGCCTCTTCGATAATGATGATGGAGACACCTATTTGGACTGGTACCTGCAGAA GCCAGGGCAGTCTCCACAACTCCTGATCTATACGCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG GTTCAGTGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT TGGAGTTTATTACTGCATGCAACGTTTAGAGTTTCCGATCACCTTCGGGCAAGGGACACGACTGGAG ATTAAACGA 60G5.1 V_(L)74 1865GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTATAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAACTATTTAA ATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTAGGCTCCTGATCTATGCAGCTTCCAGTTTGCAAAG TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG CAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTCCAGTATCCCTTGGACGTTCGGCCAAG GGACCAAGGTGGAAATCAAACGA 50D4 V_(L)92500 GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCGAGTCAGGACATTAGCAATTATTTAG CCTGGTATCAGCAGAAACCAGGGAAAGTTCCTACGCTCCTGATCTATGCTGCATCCACTTTGCTATC AGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCT GCAGCCTGAAGATGTTGCAGCTTATTACTGTCAAAAGTATTACAGTGCCCCTTTCACTTTCGGCCCT GGGACCAAAGTGGATATCAACCGA 50G5v1V_(L)93 501 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACTATCACTT GCCGGGCAAGTCAGGGCATTAGAAATGATTTAGGCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA ACCGCCTGATCTATGCTGCGTCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC TGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCTA CAGCATAATAGTTACCCTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGA 50G5v2 V_(L)94 502GATGTTGTGATGACTCAGTGTCCACTCTCCCTGC CCGTCACCCTTGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGACTCGTATACAGTGATGG AAACACCTACTTGAATTGGGTTCAGCAGAGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGT TTCTAACTGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACT GAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGGGTTAATTACTGCATGGAAGGTACACACTGGCC TCGGGACTTCGGCCAAGGGACACGACTGGAGATTAAACGA 51C1 V_(L)95 503 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTATAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGAGCATTAGCAACTATTTAAATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTA GACTCCTGATCTATGCAGCTTCCAGTTTGCAAAGTGGGGTCCCATCGAGGTTTAGTGGCAGTGGATC TGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAAC AGAGTTCCAGTATCCCTTGGACGTTCGGCCAAGGGACCACGGTGGAAATCAAACGA 53C3.2 V_(L)96 504GACATAGTGATGACGCAGTCTCCAGCCACCCTG TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTATTAGCAGCAATTTAG CCTGGTACCAGCAGACACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTACATCCATCAGGGCCA GTACTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCC TGCAGTCTGAAGATTTTGCAATTTATTACTGTCACCAGTATACTAACTGGCCTCGGACGTTCGGCCA AGGGACCAAGGTGGAAATCAAACGA 54H10.3V_(L)97 505 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTT GCCGGGCAAGTCAGACCATTAGCATCTATTTAAATTGGTATCAGCAAAAACCAGGGAAAGCCCCTA AGTTCCTGATCTATTCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC TGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTTCAACTTACTTCTGTCAAC AGAGTTACAGTTCCCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGA 55A7 V_(L)98 506GACATCCAGATGACCCAGTCTCCATCCTCCCTGT CTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAA ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAG TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG CAACCTGAAGATTTTGCAACTTACTACTGTCAACAGACTTACAGTGCCCCATTCACTTTCGGCCCTGG GACCAAAGTGGATATCAAACGA 55E6 V_(L)99507 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGTCGCAGCCACT TAGCCTGGTACCAGCAGAACTCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGG CCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCA GACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGTTCACCGTGGACGTTCG GCCAAGGGACCAAGGTGGAAATCAAACGA 61E1V_(L)100 508 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTATTAGAGACCGAGTCACCATCACTTG CCGGGCAAGTCAGAGCATTGGCACCTTTTTAAATTGGTATCAGCAGAAACCAGGGACAGCCCCTAA GCTCCTGATCTATGCTGCGTCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCT GGGACAGATTTCACTCTCACCATCAGCAGTCTACATCCTGAAGATTTTGCGTCTTACTATTGTCAAC AGAGTTTCAGTACCCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCACACGA

TABLE 2D Coding Sequence for Antibody Variable Heavy (V_(H)) ChainsContained SEQ ID in Clone Designation NO. Coding Sequence 63E6 V_(H) 6509 CAGGTGCAGCTTATGCAGTCTGGGGCTGAGGTG 66F7AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGC TTGAGTGGATGGGATGGATGAACCCTAATAGTGGTGCCACAAAGTATGCACAGAAGTTTCAGGGCA GGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTG ACGACACGGCCGTGTATTACTGTGCGAGAGAACTCGGTGACTACCCCTTTTTTGACTACTGGGGCCA GGGAACCCTGGGCATCGTCTCCTCA 66D4V_(H)17 510 CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTC TCCTGCAGGGCTTCTGGGTACACCTTCACCGGCTACTATATACACTGGATGCGACAGGCC CCTGGCCATGGGCTGGAGTGGATGGGATGGATCAACCCTCCCAGTGGTGCCACAAACTAT GCACAGAAGTTTCGGGGCAGGGTCGCCGTGACCAGGGACACGTCCATCAGCACAGTCTAC ATGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTATATTACTGTGCGAGAGAGACT GGAACTTGGAACTTCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 66B4 V_(H)10 511CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCATCTGGATACACCTTCACCGGCTACTATT TGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTG GTGGCACAGACTATGCACAGAAGTTTCAGGGCCGGGTCACCATGACCAGGGACACGTCCATCAGTA CAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGTGGGAGACG CAGCAACTGGTCGCTACTACTTTGACAACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65B1 V_(H)18 512CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG AAGAGGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTTTA TGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTG GTGCCACAAACTATGCACAGAAGTTTCACGGCAGGGTCACCATGACCAGGGACACGTCCATCACCA CAGTCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTACGAGAGAAC TGGGGATCTTCAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65B4 V_(H)20 513GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTG GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCGCCTTCAGTAGTTACGACA TGCACTGGGTCCGCCAAGCTACAGGAAAAGGTCTGGAGTGGGTCTCAACTATTGATACTGCTGGTG ACGCTTACTATCCAGGCTCCGTGAAGGGCCGATTCACCATCTCCAGAGAAAATGCCAAGACCTCCT TGTATCTTCAAATGAACAGCCTGAGAGCCGGGGACACGGCTGTGTATTACTGTACAAGAGATCGGA GCAGTGGCCGGTTCGGGGACTTCTACGGTATGGACGTCTGGGGCCAAGGGACCGCGGTCACCGTCT CCTCA 67A4 V_(H)19 514GAGGTGCAGCTGGAGGAGTCTGGGGGAGGCTTG GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGGACCTACGAC ATGCACTGGGTCCGCCAAGTTACAGGAAAAGGTCTGGAGTGGGTCTCAGCTATTGGTATTGCTGGTG ACACATACTATTCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGAAAATGCCAAGAACTCCC TGTATCTTCAAATGAACAGTCTAAGAGTCGGGGACACGGCTGTGTATTACTGTGCAAGAGATCGGA GCAGTGGCCGGTTCGGGGACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCT CCTCA 63A10v1 V_(H)21 515GAGGTGCAGCTGGTGGAGTCTGGGGGAGACTTG 63A10v2GTAAAGCCTGGGGGGTCCCTTAGACTCTCCTGT 63A10v3GCAGTCTCTGGAATCACTTTCAGTAACGCCTGG ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTTGGCCGTATTAAAAGCAAAACT GATGGTGGGACAACAGACTACGCTGCACCCGTGAAAGGCAGATTCACCGTCTCAAGAGATGGTTCA AAAAATACGCTGTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTACC ACAGATAGTAGTGGGAGCTACTACGTGGAGGACTACTTTGACTACTGGGGCCAGGGAACCCTGGTC ACCGTCTCCTCA 65H11v1 V_(H)22 516GAGGTGCAACTGGTGGAGTCTGGGGGAGGCTTG 65H11v2GTAAAGCCTGGGGGGTCCCTTAGACTCTCCTGT GCAGCCTCTGGATTCACTTTCAGTAACGCCTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGC TGGAGTGGGTTGGCCGTATTATAGGCAAAACTGATGGTGGGACAACAGACTACGCTGCACCCGTGA AAGGCAGATTCACCATTTCAAGAGATGATTCAAAAAACACGCTGTATCTGCAAATGAACAGCCTGA AAACCGAGGACACAGCCGTGTATTACTGTACCTCAGATAGTAGTGGGAGCTACTACGTGGAGGACT ACTTTGACTACTGGGGCCAGGGAACCCTGGTCGCCGTCTCCTCA 67G10v1 V_(H)9 517 GAGGTGCAACTGGTGGAGTCTGGGGGAGGCTTG 67G10v2GTAAAGCCGGGGGGGTCCCTTAGACTCGCCTGT GCAGCCTCTGGAATCACTTTCAATAACGCCTGGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGG CTGGAATGGGTTGGCCGTATTAAAAGCAAAACTGATGGTGGGACAACAGACTACGCTGCACCCGTG AAAGGCAGATTCACCATCTCAAGAGATGATTCAAAAAGTATACTGTATCTGCAAATGAACAGCCTG AAATCCGAGGACACAGCCGTGTATTATTGTACCACAGATAGTAGTGGGAGCTACTACGTGGAGGAC TACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 64C8 V_(H)23 518 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GTAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGATCCAGGCAAGGGGC TGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAACAAACACTATGCAGACTCCGTGAAGGGCC GATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTG AGGACACGGCTGTGTATTACTGTGCGAGGGAATTACTATGGTTCGGGGAGTATGGGGTAGACCACG GTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 63G8v1 V_(H)1 519 CAGGCGCAGCTGGTGGAGTCTGGGGGAGGCGTG 63G8v2GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT 63G8v3GCAGCCTCTGGATTCACCTTCAGTAGCTATGGCA 68D3v1TACACTGGGTCCGCCAGGCTCCAGGCAAGGGGC 64A8 TGGAGTGGGTGGCAGTTATATCATATGATGGAA67B4 GTAATAAATACTATGCAGACTCCGTGAAGGGCC GATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTG AGGACACGGCTGTGTATTACTGTGCGACTACGGTGACTAAGGAGGACTACTACTACTACGGTATGG ACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 68D3v2 V_(H)95 1866 CAGGCGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTC TCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCT CCAGGCAAGGGGCTGGAGTGGGTGGCATTTATATCATATGCTGGAAGTAATAAATACTAT GCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT CTGCAAATGAGCAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGACTACGGTG ACTGAGGAGGACTACTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACC GTCTCCTCA 66G2 V_(H)11 520CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCAGGATTCACCTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGGTATATCATATGATGGA AGTAATAAAAACTATGCAGACTCCGTGAAGGGCCGAATCACCATCTCCAGAGACAATCCCAAGAAC ACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGACTACG GTGACTAAGGAGGACTACTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTC TCCTCA 65D1 V_(H)26 521CAGGTGCAACTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTTACTATTACA TTCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATGGTATGATGGAA GTAATAAAGACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTGCATGTGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAAG GGACAACTCGACGGGGATTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 64H5 V_(H)7 522CAGGTGCAGCTGGTGGAGTCTGGGGGAGGAGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGGATGATGGA AGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTGTCTCTGCAAATGAACAGCCTGAGGGCCGAGGACACGGCTGTTTATTACTGTGCGAGAGAA TACGTAGCAGAAGCTGGTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65D4 V_(H)25 523CAGGAGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGTGTCTGGATTCACCTTCAGTTTCTATGGCA TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAA GTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATTTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTACGAGAGCCC TCAACTGGAACTTTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65E3 V_(H)24 524CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCCTCAGTAACTATAAC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTTTATGGTATGATGGA AATACTAAATACTATGCAGACTCCGTGAAGGGCCGAGTCACCATCTCTAGAGACAATTCCAAGAAC ACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAT GTCTACGGTGACTATTTTGCGTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65G4 V_(H)8 525CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGGATGATGGA AGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTGTCTCTGCAAATGAACAGCCTGAGGGCCGAGGACACGGCTGTTTATTACTGTGCGAGAGAA TACGTAGCAGAAGCTGGTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 68G5 V_(H)12 526CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTACAGCGTCTGGATTCACCTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGA AGTAATAAATACCATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACGATTCCAAGAAC GCGCTTTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGTGAGAGAT CCTGGATACAGCTATGGTCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 67G8 V_(H)27 527CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGA AGTAATAAAGACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATCA GCAGTGGCTTTGTACAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65B7v1 V_(H)28 528CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG 65B7v2GTGAACCCTTCACAGACCCTGTCCCTCACCTGCA CTGTCTCTGGTGGCTCCATCAGCAGTGATGCTTACTACTGGAGCTGGATCCGCCAGCACCCAGGGAA GGGCCTGGAGTGGATTGGGTACATCTTTTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAG TCGAGTTACCATTTCAGTAGACACGTCTAAGAACCGGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC GCGGACACGGCCGTGTATTACTGTGCGAGAGAGTCTAGGATATTGTACTTCAACGGGTACTTCCAGC ACTGGGGCCAGGGCACCCTGGTCACCGTCTCCT CA63B6 V_(H)4 529 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG 64D4GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCG CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTACTACTGGAGCTGGATCCGCCAGCACCCAGGGAA GGGCCTGGAGTGGATTGGGTACATCTATTACAGTGGGACCACCTACTACAACCCGTCCCTCAAGAG TCGAGTTACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGACCTCTGTGACTGCC GCGGACACGGCCGTATATTACTGTGCGAGAATGACTACTCCTTACTGGTACTTCGGTCTCTGGGGCC GTGGCACCCTGGTCACTGTCTCCTCA 63F5V_(H)13 530 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTATTACTGGACCTGGATCCGCCAGCACCCAGGGAA GGACCTGGAGTGGATTACATACATCTATTACAGTGGGAGCGCCTACTACAACCCGTCCCTCAAGAG TCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC GCGGACACGGCCGTATATTATTGTGCGAGGATGACTACCCCTTATTGGTACTTCGATCTCTGGGGCC GTGGCACCCTGGTCACTGTCTCCTCA 63H11V_(H)3 531 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTACTACTGGACCTGGATCCGCCAGCACCCAGGGAA GGGCCTGGAGTGGATTGCATACATCTATTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAG TCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC GCGGACACGGCCGTATATTACTGTGCGAGGATGACTACCCCTTACTGGTACTTCGATCTCTGGGGCC GTGGCACCCTGGTCACTGTCTCCTCA 65E8V_(H)2 532 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG 64E6GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC 65F11CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA 67G7CTACTGGACCTGGATCCGCCAGCACCCAGGGAA GGGCCTGGAGTGGATTGCATACATCTATTACACTGGGAGCACCTACTACAACCCGTCCCTCAAGAG TCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC GCGGACACGGCCGTATATTACTGTGCGAGGATGACTACCCCTTACTGGTACTTCGATCTCTGGGGCC GTGGCACCCTGGTCACTGTCTCCTCA 65C1V_(H)15 533 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTACTACTGGACCTGGATCCGCCAACACCCAGGGAA GGGCCTGGAGTGGATTGCATACATTTTTTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAGT CGAGTTACCATATCACTTGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAACTCTGTGACTGCCG CGGACACGGCCGTATATTACTGTGCGAGGATGACTTCCCCTTACTGGTACTTCGATCTCTGGGGCCG TGGCACCCTGGTCACTGTCTCCTCA 66F6V_(H)14 534 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTACTACTGGACCTGGATCCGCCATCACCCAGGGAA GGGCCTGGAGTGGATTGCATACATTTATTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAG TCGAGTTACCATATCAGTTGACACGTCTAAGAACCAGTTTTCCCTGAAGCTGAACTCTGTGACTGCC GCGGACACGGCCGTTTATTACTGTGCGAGGATGACTACCCCTTACTGGTACTTCGATCTCTGGGGCC GTGGCACCCTGGTCACTGTCTCCTCA 64A6V_(H)29 535 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA CTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTATTACTGGAGCTGGATCCGCCAGCGCCCAGGGAA GGGCCTGGAGTGGGTTGGGTACATCTATTACAGTGGGGGCACCCACTACAACCCGTCCCTCAAAAG TCGAGTTACCATATCAATAGACACGTCTGAGAACCAGTTCTCCCTGAAGCTGAGTTCTGTGACTGCC GCGGACACGGCCGTGTATTACTGTGCGAGAGTCCTCCATTACTCTGATAGTCGTGGTTACTCGTACT ACTCTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 65F9 V_(H)30 536 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA CTCTCTCTGGTGGCTCCTTCAGCAGTGGTGATTACTACTGGAGCTGGATCCGCCAGCACCCAGGGAA GGGCCTGGAGTGGATTGGGTACATCTATTACAGTGGGAGCACCTACTACAACCCATCCCTCAAGAG TCGAGTTACCATATCAATAGACACGTCTAAGAACCAGTTCTCCCTGAAACTGACCTCTGTGACTGCC GCGGACACGGCCGTGTATTACTGTGCGAGAGTCCTCCATTACTATGATAGTAGTGGTTACTCGTACT ACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 64A7 V_(H)16 537 CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC ACTGTCTCTGGTGGCTCCATCAGCAGTGATACTTCCTACTGGGGCTGGATCCGCCAGCCCCCAGGAA AGGGGCTGGAGTGGATTGGGAATATCTATTATAGTGGGACCACCTACTTCAACCCGTCCCTCAAGA GTCGAGTCAGCGTATCCGTAGACACATCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC CGCAGACACGGCTGTGTTTTATTGTGCGAGACTCCGAGGGGTCTACTGGTACTTCGATCTCTGGGGC CGTGGCACCCTGGTCACTGTCTCCTCA 65C3V_(H)5 538 CAGGTGCAGCTACAGGAGTCGGGTCCAGGACTG 68D5GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC ACTGTCTCTGGTGGCTCCATCAGTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA CTGGAGTGGATTGGGTATATCTATTACACTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA GTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGG ACACGGCCGTGTATTACTGTGCGAGAGAATATTACTATGGTTCGGGGAGTTATTATCCTTGGGGCCA GGGAACCCTGGTCACCGTCTCCTCA 67F5V_(H)31 539 CAGGTGCAGCTGAAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTC ACCTGCACTGTCTCTGGTGGCTCCATCAGTAGTTACTACTGGAGCTGGATCCGGCAGCCC CCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAACACCAACTACAAC CCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTG AAGCTGAGCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGAGAGAATATTAC TATGGTTCGGGGAGTTATTATCCTTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 64B10v1 V_(H)32 540CAGATTCAGCTGCTGGAGTCGGGCCCAGGACTG GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCGTCAGTAGTGGTGATT ACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGTTTATCTATTACA GTGGGGGCACCAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGA ACCAGTTCTCCCTGAAGCTGAACTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGAGATA TAGCAGCACCTGGGACTACTATTACGGTGTGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTC CTCA 64B10v2 V_(H)96 1867CAGGTGCAGCTGCTGGAGTCGGGCCCAGGACTG GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCGTCAGCAGTGGTGATT ACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGTTTATTTATTACA GTGGGGGCACCAACTACAACCCCCCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGA ACCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGAGATA TAGCAGCACCTGGGACTACTATTACGGTGTGGACGTCTGGGGCCAAGGGACCACGGTCACC GTCTCCTCA 68C8 V_(H)33 541CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGACTCTGTCAGCAGTGGTGATA ACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGTTCATGTTTTACA GTGGGAGTACCAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCACTACACACGTCCAAGA ACCAGTTCTCCCTGAGGCTGAGCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGGGAGATA TAGGAGTGACTGGGACTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTC CTCA 67A5 V_(H)34 542GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGTTACTGG ATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGAC TCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAAC ACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATATACTTCTGTGCGAGACGG GCCTCACGTGGATACAGATTTGGTCTTGCTTTTGCGATCTGGGGCCAAGGGACAATGGTCACCGTCT CCTCA 67C10 V_(H)35 543GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTCAGGGTTCTGGATACAGCTTTAGCAGTTACTGG ATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGAC TCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAAT ACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATATATTACTGTGCGAGACGG GCCTCACGTGGATACAGATATGGTCTTGCTTTTGCTATCTGGGGCCAAGGGACAATGGTCACCGTCT CTTCA 64H6 V_(H)36 544GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGTTTTACCAGTTATTGGA TCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACT CTGAAACCAGATACAGCCCGTCCTTTCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCA CCGCCTACCTGCAGTGGAACAGCCTGAAGACCTCGGACACCGCCATGTATTTCTGTGCGACCGTAG CAGTGTCTGCCTTCAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCC 63F9 V_(H)37 545CAGGTGCAGCTGAAGGAGTCGGGCCCAGGACTG GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTA CTACTGGAACTGGATCCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGGTACATCTATGACAG TGGGAGCACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATGTCAGTAGACACGTCTAAGAA CCAGTTCTCCCTGAAGTTGAGCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGAT GTTCTAATGGTGTATACTAAAGGGGGCTACTACTATTACGGTGTGGACGTCTGGGGCCAAGGGACC ACGGTCACCGTCTCCTCA 67F6v1 V_(H)38 546GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG 67F6v2AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT AAGGGTTCTGGATACAGCTTTACCGGCTACTGGATCGGCTGGGTGCGCCAGCTGCCCGGGAAAGGC CTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGC CAGGTCACCATCTCAGTCGACAAGTCCATCAACACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCC TCGGACACCGCCATGTATTACTGTGCGAGACGGGCCTCACGTGGATACAGCTATGGTCATGCTTTTG ATTTCTGGGGCCAAGGGACAATGGTCACCGTGTCTTCA 48C9 V_(H)73 547 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG 49A12TTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCT 51E2CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG GACCTGGATCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGAAAA CACCAACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGAACCAGTT CTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGAGAGTGG GAACTTCCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 48F3 V_(H)72 548 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACCGTTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCG CTGTCTATGGTGGGTCCATCAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCAGGGAAGGGGCT GGAGTGGATTGGGGAAATCACTCATACTGGAAGCTCCAACTACAACCCGTCCCTCAAGAGTCGAGT CACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGA CACGGCTGTGTATTACTGTGCGAGAGGCGGGATTTTATGGTTCGGGGAGCAGGCTTTTGATATCTGG GGCCAAGGGACAATGGTCACCGTCTCTTCA 48F8V_(H)48 549 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG 53B9GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT 56B4 ACAGCCTCTGGATTCACCTTCAGAAGCTATAGC57E7 ATGAACTGGGTCCGCCAGGCTCCGGGGAAGGGG 57F11CTGGAGTGGGTCTCATCCATTAGTAGTAGTAGT AGTTACGAATACTACGTAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACATCGCCAAGAGC TCACTGTGGCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATCC CTAAGTATAGCAGTGGCTGCCTCTGACTACTGGGGCAAGGGAACCCTGGTCACCGTCTCCTCA 48H11 V_(H)39 550CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTG AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATA AGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTG GTGCCACAAAGTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCA CAGTGTACATGGAGCTGAGCAGGCTGAGATCTGTCGACACGGCCCTGTATTACTGTGCGAGAGAGG TACCCGACGGTATAGTAGTGGCTGGTTCAAATGCTTTTGATTTCTGGGGCCAAGGGACAATGGTCA CCGTCTCTTCA 49A10 V_(H)62 551CAGGTGCACCTGGTGGAGTCTGGGGGAGGCGTG 48D4 GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAACTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAATTATATGGTATGATGGA AGTAATAAAAACTATGCAGACTCCGTGAAGGGCCGCTTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTGTATCTGGAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAT CAGGATTACGATTTTTGGAGTGGTTATCCTTACTTCTACTACTACGGTATGGACGTCTGGGGCCAAG GGACCACGGTCACCGTCTCCTCA 49C8 V_(H)44552 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG 52H1AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCTTCTGGATACACCTTCACCAGTTATGATATCGACTGGGTGCGACAGGCCACTGGACAAGGGC TTGAGTGGATGGGATGGATGAACCCTAACGGTGGTAACACAGGCTATGCACAGAAGTTCCAGGGCA GAGTCACCATGACCAGGAACACCTCCATAAACACGGCCTATATGGAACTGAGCAGCCTGAGATCTG AGGACACGGCCATATATTACTGTGCGAGAGGGAAGGAATTTAGCAGGGCGGAGTTTGACTACTGGG GCCAGGGAACCCTGGTCACCGTCTCCTCA 49G2V_(H)63 553 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG 50C12GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT 55G11GCAGCGTCTGGATTCACCTTCAGTAACTATGGC ATGCGCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATGGTATGATGGA AGTAATAAGTTCTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTGAATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAT CGGTATTACGATTTTTGGAGTGGTTATCCATACTTCTTCTACTACGGTCTGGACGTCTGGGGCCAAG GGACCACGGTCACCGTCTCCTCA 49G3 V_(H)46554 CAGGTCACCTTGAAGGAGTCTGGTCCTGTGCTG GTGAAACCCACAGAGACCCTCACGCTGACCTGCACCGTCTCTGGGTTCTCACTCAGTAATCCTAGAA TGGGTGTGAGCTGGATCCGTCAGCCCCCAGGGAAGGCCCTGGAGTGGCTTACACACATTTTTTCGAA TGACGAAAAATCCTACAGCACATCTCTGAAGAGCAGGCTCACCATCTCCAAGGACACCTCCAAAAG CCAGGTGGTCCTTTCCATGACCAACATGGACCCTGTGGACACAGCCACATATTACTGTGTACGGGTA GATACCTTGAACTACCACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCC TCA 49H12 V_(H)42 555CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCATGGCATCTGGATACATTTTCACCAGTTACGATA TCAACTGGGTGCGACAGGCCACTGGACAAGGGCCTGAGTGGATGGGATGGATGAACCCCTACAGTG GGAGCACAGGCTATGCACAGAATTTCCAGGGCAGAGTCACCATGACCAGGAATACCTCCATAAACA CAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAAGTATA ATTGGAACTATGGGGCTTTTGATTTCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA 51A8 V_(H)58 556CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCA TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAA GTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGTTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGCGG ACGGTGACTACCCATATTACTACTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCAC CGTCTCCTCA 51C10.1 V_(H)54 557GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG 59D10v1GTACAGCCGGGGGGGTCCCTGAGACTCTCCTGT 59D10v2GCAGCCTCTGGATTCACCTTTCGCAACTATGCCA TGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTAGTGGTAGTAGTG CTGGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTTTCTGCAAATGGACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGCAAGATT GGAGTATAGCAGTGGCTGGTACTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 51C10.2 V_(H)67 558CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTA CTACTGGAGCTGGATCCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACAA TGGGAGTCCCTACGACAACCCGTCCCTCAAGAGGCGAGTTACCATCTCAATAGATGCGTCTAAGAA CCAGTTCTCCCTGAAGCTGAGCTCTATGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGGG GCCCTCTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 51E5 V_(H)74 559 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTTTCCCTCACCTGCG CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCAGGGAAGGGGCT GGAGTGGATTGGGGAACTCGATCATAGTGGAAGTATCAACTACAACCCGTCCCTCAAGAGTCGAGT CACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGACCTCTGTGACCGCCGCGGA CACGGCTGTGTATTACTGTGCGAGAGTCCTGGGATCTACTCTTGACTATTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 51G2 V_(H)50 560GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGTTATAGCA TGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCATCCATTAGTAGTAGTAGTA CTTACATATACTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACT CACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATA CTTATATCAGTGGCTGGAACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCT CA 52A8 V_(H)40 561CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATT TGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTG CTGCCACAAACTATGCACCGAAGTTTCAGGGCAGGGTCACCGTGACCAGGGACACGTCCATCAGCA CAGCCTACATGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGAGG GTGGAACTTACAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 52B8 V_(H)77 562CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG ATGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGTTATTATTACT GGAGTTGGATCCGGCAGTCCCCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTATAGTGGGA GCACCAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGT TCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGTGCGTCTGGAACTA GGGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA 52C1 V_(H)64 563 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGC CTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAACTATTATGCAGACTCCGTGAAGGGC CGATTCACCATCTCCAGAGACAATTCCAAGAGCACGCTGTTTCTGCAAATGAACAGCCTGAGAGCC GAGGACACGGCTATATATTACTGTGCGAGAGATCGGGCGGGAGCCTCTCCCGGAATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCA 52F8V_(H)41 564 CAGGTGCAACTGGTGCAGTCTGGGGCGGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCTTCTGGATTCACCTTCATCGGCTACTATACACACTGGGTGCGACAGGCCCCTGGACAAGGGC TTGAGTGGATGGGATGGATCAACCCTAGCAGTGGTGACACAAAGTATGCACAGAAGTTTCAGGGCA GGGTCACCTTGGCCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTG ACGACACGGCCGTGTATTACTGTGCGAACAGTGGCTGGTACCCGTCCTACTACTACGGTATGGACGT CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA52H2 V_(H)79 565 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC ACTGTCTCTGGTGGCTCCATCAGTACTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGACGGGAC TGGAATGGATTGGGTATATCTTTTACAATGGGAACGCCAACTACAGCCCCTCCCTGAAGAGTCGAG TCACCTTTTCAGTGGACACGTCCAAGAACCAGTTCTCCCTGAAACTGAGTTCTGTGACCGCTGCGGA CACGGCCGTGTATTTTTGTGCGAGAGAAACGGACTACGGTGACTACGCACGTCCTTTTGAATACTGG GGCCAGGGAACCCTGGTCACCGTCTCCTCA 53F6V_(H)60 566 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GCAGCGTCTGGATTCACCTTCAGTACCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC TGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCC GATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCG AGGACACGGCTGTGTATTACTGTGCGAGAGGCCACTATGATAGTAGTGGTCCCAGGGACTACTGGG GCCAGGGAACCCTGGTCACCGTCTCCTCA 53H5.2V_(H)59 567 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCCAGGGGC TGGAGTGGGTGGCACTTATATCATATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCC GATTCACCATCTCCAGAGACAAATCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTG AGGACACGGCTGTATATTACTGTGCGAGAGAGGCTAACTGGGGCTACAACTACTACGGTATGGACG TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT CA53H5.3 V_(H)75 568 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCG CTGTCTATGGTGGGTCCTTCAGTGATTACTACTGGAACTGGATCCGCCAGCCCCCAGGGAAGGGGCC AGAGTGGATTGGGGAAATCAATCATAGTGGAACCACCAACTACAATCCGTCCCTCAAGAGTCGAGT CACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGA CACGGCTGTATATTACTGTGTGGGGATATTACGATATTTTGACTGGTTAGAATACTACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA54A1 V_(H)43 569 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG 55G9AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCTTCTGGATACACCTTCACCAGTTATGATATCAACTGGGTGCGACAGGCCACTGGACAAGGGC TTGAGTGGATGGGATGGATGAACCCTCACAGTGGTAACACAGGCTATGCACAGAAGTTCCAGGGCA GAGTCACCATGACCAGGAACACCTCCATAAATACAGCCTACATGGAGCTGAGCAGCCTGAGATCTG AGGACACGGCCGTGTATTACTGTGCGAAATATAACTGGAACTACGGCGCTTTTGATTTCTGGGGCCA AGGGACAATGGTCACCGTCTCTTCA 54H10.1V_(H)52 570 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG 55D1GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT 48H3GCAGCCTCTGGATTCACCTTTAGCAGCTATGCCA 53C11TGAGCTGGGTCCGCCAGGCTCCGGGGAAGGGGC TGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTCGTACCACATACTCCGCAGACTCCGTGAAGGGCC GGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCG AGGACACGGCCGTATATTACTGTGCGAAAGAACAGCAGTGGCTGGTTTATTTTGACTACTGGGGCCA GGGAACCCTGGTCACCGTCTCCTCA 55D3V_(H)68 571 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA CTGTCTCTGGTGGCTCCATCACCAGTGGTGTTTACTACTGGAACTGGATCCGCCAGCACCCAGGGAA GGGCCTGGAGTGGATTGGGTACCTCTATTACAGTGGGAGCACCTACTACAACCCGTCCCTCAAGAG TCGCCTTACCATTTCAGCAGACATGTCTAAGAACCAGTTCTCCCTAAAGCTGAGCTCTGTGACTGTCG CGGACACGGCCGTGTATTACTGTGCGAGAGATGGTATTACTATGGTTCGGGGAGTTACTCACTACTA CGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 55E4 V_(H)70 572 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG 49B11TTGAAGCCTTCGGAGACCCTGTCCCTCACTTGCG 50H10CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG 53C1GAGCTGGATCCGCCAGCCCCCAGGGAAGGGTCT 52C5 GGAGTGGATTGGGGAAATCAATCATAGTGAAAA60G5.1 CACCAACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAATGACCAGTT CTCCCTAAGACTAACCTCAGTGACCGCCGCGGACACGGCTGTCTATTACTGTGCGAGAGTAACTGG AACGGATGCTTTTGATTTCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA 55E9 V_(H)65 573 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GCAGCGTCTGGATTCACCTTCAGTAGCTTTGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC TGGAGTGGGTGGCACTTATATGGTATGATGGAGATAATAAATACTATGCAGACTCCGTGAAGGGCC GATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCG AGGACACGGCTGTGTATTACTGTGCGAGAAACAGTGGCTGGGATTACTTCTACTACTACGGTATGGA CGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 55G5 V_(H)78 574 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC ACTGTCTCTGGTGGCTCCATCAGTAGTTACTACTGGAGCTGGATCCGGCAGCCCGCCGGGAAGGGA CTGGAGTGGATTGGGCGTATCTATATCAGTGGGAGCACCAACTACAACCCCTCCCTCGAGAATCGA GTCACCATGTCAGGAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAATTCTGTGACCGCCGCGG ACACGGCCGTATATTACTGTGCGGGAAGTGGGAGCTACTCCTTTGACTACTGGGGCCAGGGAACCC TGGTCACCGTCTCCTCA 50G1 V_(H)84 575CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCC TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGAATGATGGAA GTAATAAGCTTTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATC AGTATTACGATTTTTGGAGCGGTTACCCATACTATCACTACTACGGTATGGACGTCTGGGGCCAAGG GACCACGGTCACCGTCTCCTCA 56A7 V_(H)51576 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG 56E4GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT GCAGCCTCTGGATTCACCTTCAGTAGTTATAGCATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGC TGGAGTGGGTCTCATCCATTAGTAGTAGTAGTACTTACATATACTACGCAGACTCAGTGAAGGGCC GATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCG AGGACACGGCTGTGTATTACTGTGCGAGAGATATCTATAGCAGTGGCTGGAGCTACGGTATGGACG TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT CA56C11 V_(H)61 577 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGA CTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTTATCAATTCTATGCAGACTCCGTGAAGGGC CGATTCACCATCTCCAGAGACAATTCCAAGAACACGTTGTATCTGCAAATGAACAGCCTGAGAGCC GAGGACACGGCTGTGTATTACTGTGCGAGAGATCACGTTTGGAGGACTTATCGTTATATCTTTGACT ACTGGGGCCAGGGAACCCTGGTCACCGTCTCCT CA56E7 V_(H)81 578 GAGGTGCAGCTGGTGCAGTCTGGACCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT AAGGGTTCGGGATACAGTTTAACCAGCTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGC CTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGC CAGGTCACCATCTCAGCCGACACGTCCATCAGCACCGCCTACCTGCAGTGGAGCAGGTTGAAGGCC TCGGACACCGCCGTATATTACTGTGCGAGGGCACAACTGGGGATCTTTGACTACTGGGGCCAGGGA ACCCTGGTCACCGTCTCCTCA 56G1 V_(H)71 579CAGGTGCAACTACAGCAGTGGGGCGCAGGACTG TTGAAGCCTTCGGAGACCCTGTCCCTCACTTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG GAGCTGGATCCGCCAGCCCCCAGGGAAGGGTCTGGAGTGGATTGGGGAAATCAATCATAGTGAAAA CACCAACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAATAAGCAGTT CTCCCTAAGACTAACCTCTGTGACCGCCGCGGACACGGCTGTCTATTACTGTGCGAGAGTAACTGG AACGGATGCTTTTGATTTCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA 56G3.3 V_(H)76 580 CAGTTGCAGTTGCAGGAATCGGGCCCAGGACTG55B10 GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGACTCCATCAGTAGTAGTAGTT ACTACTGGGGCTGGATCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGATGATCTATTATA GTGGGACCACCTACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCCGTAGACACGTCCAAGA ATCAGTTTTCCCTGAAGCTGAGTTCTGTGACCGCCGCAGACACGGCTGTGTATTATTGTGCGAGAGT GGCAGCAGTTTACTGGTATTTCGATCTCTGGGGCCGTGGCACCCTGGTCACTGTCTCCTCA 57B12 V_(H)69 581CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCACCAGTGGTGTTTA CTACTGGAGCTGGATCCGCCAGCTCCCAGGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACAG TGGGAGCACCTACTACAACCCGTCCCTCAAGAGTCGCCTTACCATATCAGCAGACACGTCTAAGAA CCAGTTCTCCCTAAAGCTGAGCTCTGTGACTGTCGCGGACACGGCCGTGTATTACTGTGCGAGAGAT GGTATTACTATGGTTCGGGGAGTTACTCACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGG TCACCGTCTCCTCA 57D9 V_(H)82 582CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTG GTGAAGCCCTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTG CTACTTGGAACTGGATCAGGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACA GGTCCAAGTGGTATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATC CAAGAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTGTGT GGGTATTGTAGTAGTACCAGCTGTTCTCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCC TCA 58C2 V_(H)85 583CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAACTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGAATGATGGA AATAACAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTATATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAT CAGAATTACGATTTTTGGAATGGTTATCCCTACTACTTCTACTACGGTATGGACGTCTGGGGCCAAG GGACCACGGTCACCGTCTCCTCA 59A10 V_(H)47584 CAGGTGCAGGTGGTGGAGTCTGGGGGAGGCTTG 49H4GTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGT GCAGCCTCTGGATTCACCTTCAGTGACTCCTACATGAGCTGGATCCGCCAGGCTCCAGGGAAGGGGC TGGAGTGGATTTCTTCCATTAGTAGTAGTGGTAGTATCGTATACTTCGCAGACTCTGTGAAGGGCCG ATTCACCATCTCCAGGGACATCGCCAAGAACTCACTGTATCTGCACATGAACAGCCTGAGAGCCGA GGACACGGCCGTGTATTACTGTGCGAGAGAGACGTTTAGCAGTGGCTGGTTCGATGCTTTTGATATC TGGGGCCAAGGGACAATGGTCACCGTCTCTTCA59C9 V_(H)49 585 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG 58A5GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT 57A4GCAGCCTCTGGATTCACCTTCAGTAGCTATAGCA 57F9TGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGGC TGGAGTGGGTCTCATCCATTAGTAGTAGTAGTACTTACATATACTACGCAGACTCACTGAAGGGCC GATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTTTCTGCAAGTGAACAGCCTGAGAGCCG AAGACTCGGCTGTGTATTACTGTGCGAGAGATCGATGGAGCAGTGGCTGGAACGAAGGTTTTGACT ATTGGGGCCAGGGAACCCTGGTCACCGTCTCCT CA59G10.2 V_(H)57 586 CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT GCAGCCTCTGGATTCACCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC TGGAGTGGGTGGCAATTACATCATATGGAGGAAGTAATAAAAATTATGCAGACTCCGTGAAGGGCC GATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTG AGGACACGGCTGTGTATTATTGTGCGAGAGAGGCCGGGTATAGCTTTGACTACTGGGGCCAGGGAA CCCTGGTCACCGTCTCCTCA 59G10.3 V_(H)53587 GAGGTGCAACTGTTGGGATCTGGGGGAGGCTTG GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAACCACTATGCCA TGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTG CTGGCACATTCTACGCGGACTCCATGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCGAGAACA CGCTGCATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTACTGTGCGAAAGATC TTAGAATAGCAGTGGCTGGTTCATTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 60D7 V_(H)66 588CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCAACTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGA AGTAATAAATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAAC ACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTTTTACTGTGCGAGAGAT CAGTATTTCGATTTTTGGAGTGGTTATCCTTTCTTCTACTACTACGGTATGGACGTCTGGGGCCAAGG GACCACGGTCACCGTCTCCTCA 60F9 V_(H)55589 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG 48B4GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT 52D6GCAGCCTCTGGATTCACCTTTAGCAGCTATGCCA TGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTAGTGACAGTGGTG GTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTACAAATGAACAGCCTGAGAGCCGAGGATACGGCCGTATATTACTGTGCGAAAGATC ATAGCAGTGGCTGGTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCT CA 60G5.2 V_(H)45 590CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTG AAGACGCCCGGGGCCTCAGTGAGGGTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAACTATGGTA TCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATG GTTACTCAAACTATGCACAGAAGTTCCAGGACAGAGTCACCATGACCACAGACACATCCACGAGCA CAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGAGG AGAAGCAGCTCGTCAAAGACTATTACTACTACGGTATGGACGTCTGGGGCCAGGGGTCCACGGTCA CCGTCTCCTCA 61G5 V_(H)56 591GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCA TGAGCTGGGTCCGCCAGTCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTAGTGGTAGTGGTG GTGACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTACAAATGAACAGCCTGAGAGCCGAGGATACGGCCGTATATTACTGTGCGAAAGATC ATACCAGTGGCTGGTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCT CA 56G3.2 V_(H)80 592CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGATGGCTCCATCAGTAGTTACTACT GGAACTGGATCCGGCAGCCCGCCGGGAAGGGACTGGAGTGGATTGGGCGTATCTATACCAGTGGG AGCACCAACTACAATCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAG TTCTCCCTGAACCTGACCTCTGTGACCGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGGCCCTC TTTGGTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 48G4 V_(H)83 593 CAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTG 53C3.1AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGTTTCCGGATACACCCTCACTGAATTATCCATACACTGGGTGCGACAGGCTCCTGGAAAAGGGC TTGAGTGGATGGGAGGTTTTGATCCTGAAGATGGTGAAACAATCTACGCACAGAAGTTCCAGGGCA GAGTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAGCAGCCTGAGATCTG AGGACACGGCCGTGTATTACTGTGCAACACATTCTGGTTCGGGGAGGTTTTACTACTACTACTACGG TATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 61H5 V_(H)86 594 CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTG 52B9GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC ACTGTCTCTGGTGGCTCCATCAGCAGTAGTAGTTACTACTGGGGCTGGATCCGCCAGCCCCCAGGGA AGGGGCTGGAGTGGATTGGGAGTATCTATTATAGTGGGACCACCTACTACAACCCGTCCCTCAAGA GTCGAGTCACCATATCCGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGC CGCAGACACGGCTGTGTATTACTGTGCGAGAGTGGCAGCAGTTTACTGGTACTTCGATCTCTGGGGC CGTGGCACCCTGGTCACTGTCTCCTCA 50D4V_(H)87 595 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGACTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCTTCTGGATACACCTTCACCAGTCATGATATCAACTGGGTGCGACAGGCCACTGGACACGGG CTTGAGTGGATGGGATGGATGAACCCTTACAGTGGTAGCACAGGCCTCGCACAGAGGTTCCAGGAC AGAGTCACCATGACCAGGAACACCTCCATAAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCT GAGGACACGGCCGTGTATTACTGTGCGAGAGACCTTAGCAGTGGCTACTACTACTACGGTTTGGACG TGTGGGGCCAAGGGACCACGGTCACCGTCTCCT CA50G5v1 V_(H)88 596 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG 50G5v2AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCCTCTGGATACCCCTTCATCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGC TTGAGTGGATGGGATGGATCAACCCTGACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCA GGGTCACCATGACCAGGGACACGTCCATCACCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTG ACGACACGGCCGTTTTTTACTGTGCGAGAGGCGGATACAGCTATGGTTACGAGGACTACTACGGTA TGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA 51C1 V_(H)89 597 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCTCACTTGCG CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCAGGGAAGGGTCT GGAGTGGATTGGGGAAATCAATCATAGTGAAAACACCAACTACAACCCGTCCCTCAAGAGTCGAGT CACCATATCACTAGACACGTCCCATGACCAGTTCTCCCTAAGACTAACCTCTGTGACCGCCGCGGA CACGGCTGTCTATTACTGTGCGAGAGTAACTGGAACGGATGCTTTTGATTTCTGGGGCCAAGGGAC AATGGTCACCGTCTCTTCA 53C3.2 V_(H)90 598CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTAATGGCTCCATCAATAGTGGTAATTA CTACTGGAGCTGGATCCGCCAGCACCCAGGAAAGGGCCTGGAGTGGATTGGGTACATCTATCACAG TGGGAGCGCCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATCAGTGGACACGTCTAAGAA CCAGTTCTCCCTAAAGCTGAGTTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAACT ACGGGTGCTTCTGATATCTGGGGCCAAGGGATAATGGTCACCGTCTCTTCA 54H10.3 V_(H)91 599 CAGGTGCAGGTAGTGCAGTCTGGGACTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC AAGGCTTCTGGATACACCTTCACAGGCTACTATATACATTGGGTGCGACAGGCCCCTGGACAAGGG CTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACTATGCACAGAAGTTTCGGGGC AGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCT GACGACACGGCCGTGTATTACTGTGCGAGAGAGGAAGACTACAGTGACCACCACTACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 55A7V_(H)92 600 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC ACTGTCTCTGGTGGCTCCATCAGTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA CTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA GTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAGGCTGAGCTCTGTGACCGCTGCGG ACACGGCCGTGTATTACTGTGCGAGAGGGATAACTGGAACTATTGACTTCTGGGGCCAGGGAACCC TGGTCACCGTCTCCTCA 55E6 V_(H)93 601GAAGTGCAGTTGGTGGAGTCTGGGGGAGGCTTG GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATAGCA TGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTGGTAGTA GTACCATATACCACGCAGACTCTGTGAAGGGCCGATTCACCATTTCCAGAGACAATGCCAAGAACT CACTGTATCTGCAAATGAACAGCCTGAGAGACGAGGACACGGCTGTGTATTACTGTGCGAGAGAAG GGTACTATGATAGTAGTGGTTATTACTACAACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCA CCGTCTCCTCA 61E1 V_(H)94 602CAGGTACAGCTACAGCAGTCAGGTCCAGGACTG GTGAAGCCCTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTG CTGCTTGGAACTGGATCAGGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACA GGTCCAAGTGGTATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCACCCCAGACACATC CAAGAACCAGTTCTCCCTGCAGCTGAAGTCTGTGACTCCCGAGGACACGGCTATTTATTACTGTGC AAGAGAGGGCAGCTGGTCCTCCTTCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTTTCCTCA

Each of the heavy chain variable regions listed in Table 2B can becombined with any of the light chain variable regions shown in Table 2Ato form an antigen binding protein. Examples of such combinationsinclude V_(H)1 combined with any of V_(L)1, V_(L)2, V_(L)3, V_(L)4,V_(L)5, V_(L)6, V_(L)7, V_(L)8, V_(L)9, V_(L)10, V_(L)11, V_(L)12,V_(L)13, V_(L)14, V_(L)15, V_(L)16, V_(L)17, V_(L)18, V_(L)19, V_(L)20,V_(L)21, V_(L)22, V_(L)23, V_(L)24, V_(L)25, V_(L)26, V_(L)27, V_(L)28,V_(L)29, V_(L)30, V_(L)31, V_(L)32, V_(L)33, V_(L)34, V_(L)35, V_(L)36,V_(L)37, V_(L)38, V_(L)39, V_(L)40, V_(L)41, V_(L)42, V_(L)43, V_(L)44,V_(L)45, V_(L)46, V_(L)47, V_(L)48, V_(L)49, V_(L)50, V_(L)51, V_(L)52,V_(L)53, V_(L)54, V_(L)55, V_(L)56, V_(L)57, V_(L)58, V_(L)59, V_(L)60,V_(L)61, V_(L)62, V_(L)63, V_(L)64, V_(L)65, V_(L)66, V_(L)67, V_(L)68,V_(L)69, V_(L)70, V_(L)71, V_(L)72, V_(L)73, V_(L)74, V_(L)75, V_(L)76,V_(L)77, V_(L)78, V_(L)79, V_(L)80, V_(L)81, V_(L)82, V_(L)83, V_(L)84,V_(L)85, V_(L)86, V_(L)87, V_(L)88, V_(L)89, V_(L)90, V_(L)91, V_(L)92,V_(L)93, V_(L)94, V_(L)95, V_(L)96, V_(L)97, V_(L)98, V_(L)99 andV_(L)100; V_(H)2 combined with any of V_(L)1, V_(L)2, V_(L)3, V_(L)4,V_(L)5, V_(L)6, V_(L)7, V_(L)8, V_(L)9, V_(L)10, V_(L)11, V_(L)12,V_(L)13, V_(L)14, V_(L)15, V_(L)16, V_(L)17, V_(L)18, V_(L)19, V_(L)20,V_(L)21, V_(L)22, V_(L)23, V_(L)24, V_(L)25, V_(L)26, V_(L)27, V_(L)28,V_(L)29, V_(L)30, V_(L)31, V_(L)32, V_(L)33, V_(L)34, V_(L)35, V_(L)36,V_(L)37, V_(L)38, V_(L)39, V_(L)40, V_(L)41, V_(L)42, V_(L)43, V_(L)44,V_(L)45, V_(L)46, V_(L)47, V_(L)48, V_(L)49, V_(L)50, V_(L)51, V_(L)52,V_(L)53, V_(L)54, V_(L)55, V_(L)56, V_(L)57, V_(L)58, V_(L)59, V_(L)60,V_(L)61, V_(L)62, V_(L)63, V_(L)64, V_(L)65, V_(L)66, V_(L)67, V_(L)68,V_(L)69, V_(L)70, V_(L)71, V_(L)72, V_(L)73, V_(L)74, V_(L)75, V_(L)76,V_(L)77, V_(L)78, V_(L)79, V_(L)80, V_(L)81, V_(L)82, V_(L)83, V_(L)84,V_(L)85, V_(L)86, V_(L)87, V_(L)88, V_(L)89, V_(L)90, V_(L)91, V_(L)92,V_(L)93, V_(L)94, V_(L)95, V_(L)96, V_(L)97, V_(L)98, V_(L)99 andV_(L)100; V_(H)3 combined with any of V_(L)1, V_(L)2, V_(L)3, V_(L)4,V_(L)5, V_(L)6, V_(L)7, V_(L)8, V_(L)9, V_(L)10, V_(L)11, V_(L)12,V_(L)13, V_(L)14, V_(L)15, V_(L)16, V_(L)17, V_(L)18, V_(L)19, V_(L)20,V_(L)21, V_(L)22, V_(L)23, V_(L)24, V_(L)25, V_(L)26, V_(L)27, V_(L)28,V_(L)29, V_(L)30, V_(L)31, V_(L)32, V_(L)33, V_(L)34, V_(L)35, V_(L)36,V_(L)37, V_(L)38, V_(L)39, V_(L)40, V_(L)41, V_(L)42, V_(L)43, V_(L)44,V_(L)45, V_(L)46, V_(L)47, V_(L)48, V_(L)49, V_(L)50, V_(L)51, V_(L)52,V_(L)53, V_(L)54, V_(L)55, V_(L)56, V_(L)57, V_(L)58, V_(L)59, V_(L)60,V_(L)61, V_(L)62, V_(L)63, V_(L)64, V_(L)65, V_(L)66, V_(L)67, V_(L)68,V_(L)69, V_(L)70, V_(L)71, V_(L)72, V_(L)73, V_(L)74, V_(L)75, V_(L)76,V_(L)77, V_(L)78, V_(L)79, V_(L)80, V_(L)81, V_(L)82, V_(L)83, V_(L)84,V_(L)85, V_(L)86, V_(L)87, V_(L)88, V_(L)89, V_(L)90, V_(L)91, V_(L)92,V_(L)93, V_(L)94, V_(L)95, V_(L)96, V_(L)97, V_(L)98, V_(L)99 andV_(L)100; and so on.

In some instances, the antigen binding protein includes at least oneheavy chain variable region and/or one light chain variable region fromthose listed in Tables 2A and 2B. In some instances, the antigen bindingprotein includes at least two different heavy chain variable regionsand/or light chain variable regions from those listed in Table 2B. Anexample of such an antigen binding protein comprises (a) one V_(H)1, and(b) one of V_(H)2, V_(H)3, V_(H)4, V_(H)5, V_(H)6, V_(H)7, V_(H)8,V_(H)9, V_(H)10, V_(H)11, V_(H)12, V_(H)13, V_(H)14, V_(H)15, V_(H)16,V_(H)17, V_(H)18, V_(H)19, V_(H)20, V_(H)21 V_(H)22, V_(H)23, V_(H)24,V_(H)25, V_(H)26, V_(H)27, V_(H)28, V_(H)29, V_(H)30, V_(H)31, V_(H)32,V_(H)33, V_(H)34, V_(H)35, V_(H)36, V_(H)37, V_(H)38, V_(H)39, V_(H)40,V_(H)41, V_(H)42, V_(H)43, V_(H)44, V_(H)45, V_(H)46, V_(H)47, V_(H)48,V_(H)49, V_(H)50, V_(H)51, V_(H)52, V_(H)53, V_(H)54, V_(H)55, V_(H)56,V_(H)57, V_(H)58, V_(H)59, V_(H)60, V_(H)61, V_(H)62, V_(H)63, V_(H)64,V_(H)65, V_(H)66, V_(H)67, V_(H)68, V_(H)69, V_(H)70, V_(H)71, V_(H)72,V_(H)73, V_(H)74, V_(H)75, V_(H)76, V_(H)77, V_(H)78, V_(H)79, V_(H)80,81, V_(H)82, V_(H)83, V_(H)84, V_(H)85, V_(H) 86, V_(H) 87, V_(H)88,V_(H)89, V_(H)90, V_(H)91, V_(H)92, V_(H)93, and V_(H)94. Anotherexample comprises (a) one V_(H)2, and (b) one of V_(H)1, V_(H)3, V_(H)4,V_(H)5, V_(H)6, V_(H)7, V_(H)8, V_(H)9, V_(H)10, V_(H)11, V_(H)12,V_(H)13, V_(H)14, V_(H)15, V_(H)16, V_(H)17, V_(H)18, V_(H)19, V_(H)20,V_(H)21 V_(H)22, V_(H)23, V_(H)24, V_(H)25, V_(H)26, V_(H)27, V_(H)28,V_(H)29, V_(H)30, V_(H)31, V_(H)32, V_(H)33, V_(H)34, V_(H)35, V_(H)36,V_(H)37, V_(H)38, V_(H)39, V_(H)40, V_(H)41, V_(H)42, V_(H)43, V_(H)44,V_(H)45, V_(H)46, V_(H)47, V_(H)48, V_(H)49, V_(H)50, V_(H)51, V_(H)52,V_(H)53, V_(H)54, V_(H)55, V_(H)56, V_(H)57, V_(H)58, V_(H)59, V_(H)60,V_(H)61, V_(H)62, V_(H)63, V_(H)64, V_(H)65, V_(H)66, V_(H)67, V_(H)68,V_(H)69, V_(H)70, V_(H)71, V_(H)72, V_(H)73, V_(H)74, V_(H)75, V_(H)76,V_(H)77, V_(H)78, V_(H)79, V_(H)80, 81, V_(H)82, V_(H)83, V_(H)84,V_(H)85, V_(H) 86, V_(H) 87, V_(H)88, V_(H)89, V_(H)90, V_(H)91,V_(H)92, V_(H)93, and V_(H)94. Yet another example comprises (a) oneV_(H)3, and (b) one of V_(H)1, V_(H)2, V_(H)4, V_(H)5, V_(H)6, V_(H)7,V_(H)8, V_(H)9, V_(H)10, V_(H)11, V_(H)12, V_(H)13, V_(H)14, V_(H)15,V_(H)16, V_(H)17, V_(H)18, V_(H)19, V_(H)20, V_(H)21 V_(H)22, V_(H)23,V_(H)24, V_(H)25, V_(H)26, V_(H)27, V_(H)28, V_(H)29, V_(H)30, V_(H)31,V_(H)32, V_(H)33, V_(H)34, V_(H)35, V_(H)36, V_(H)37, V_(H)38, V_(H)39,V_(H)40, V_(H)41, V_(H)42, V_(H)43, V_(H)44, V_(H)45, V_(H)46, V_(H)47,V_(H)48, V_(H)49, V_(H)50, V_(H)51, V_(H)52, V_(H)53, V_(H)54, V_(H)55,V_(H)56, V_(H)57, V_(H)58, V_(H)59, V_(H)60, V_(H)61, V_(H)62, V_(H)63,V_(H)64, V_(H)65, V_(H)66, V_(H)67, V_(H)68, V_(H)69, V_(H)70, V_(H)71,V_(H)72, V_(H)73, V_(H)74, V_(H)75, V_(H)76, V_(H)77, V_(H)78, V_(H)79,V_(H)80, 81, V_(H)82, V_(H)83, V_(H)84, V_(H)85, V_(H) 86, V_(H) 87,V_(H)88, V_(H)89, V_(H)90, V_(H)91, V_(H)92, V_(H)93, and V_(H)94, etc.Still another example of such an antigen binding protein comprises (a)one V_(L)1, and (b) one of V_(L)2, V_(L)3, V_(L)4, V_(L)5, V_(L)6,V_(L)7, V_(L)8, V_(L)9, V_(L)10, V_(L)11, V_(L)12, V_(L)13, V_(L)14,V_(L)15, V_(L)16, V_(L)17, V_(L)18, V_(L)19, V_(L)20, V_(L)21, V_(L)22,V_(L)23, V_(L)24, V_(L)25, V_(L)26, V_(L)27, V_(L)28, V_(L)29, V_(L)30,V_(L)31, V_(L)32, V_(L)33, V_(L)34, V_(L)35, V_(L)36, V_(L)37, V_(L)38,V_(L)39, V_(L)40, V_(L)41, V_(L)42, V_(L)43, V_(L)44, V_(L)45, V_(L)46,V_(L)47, V_(L)48, V_(L)49, V_(L)50, V_(L)51, V_(L)52, V_(L)53, V_(L)54,V_(L)55, V_(L)56, V_(L)57, V_(L)58, V_(L)59, V_(L)60, V_(L)61, V_(L)62,V_(L)63, V_(L)64, V_(L)65, V_(L)66, V_(L)67, V_(L)68, V_(L)69, V_(L)70,V_(L)71, V_(L)72, V_(L)73, V_(L)74, V_(L)75, V_(L)76, V_(L)77, V_(L)78,V_(L)79, V_(L)80, V_(L)81, V_(L)82, V_(L)83, V_(L)84, V_(L)85, V_(L)86,V_(L)87, V_(L)88, V_(L)89, V_(L)90, V_(L)91, V_(L)92, V_(L)93, V_(L)94,V_(L)95, V_(L)96, V_(L)97, V_(L)98, V_(L)99 and V_(L)100. Again anotherexample of such an antigen binding protein comprises (a) one V_(L)2, and(b) one of V_(L)1, V_(L)3, V_(L)4, V_(L)5, V_(L)6, V_(L)7, V_(L)8,V_(L)9, V_(L)10, V_(L)11, V_(L)12, V_(L)13, V_(L)14, V_(L)15, V_(L)16,V_(L)17, V_(L)18, V_(L)19, V_(L)20, V_(L)21, V_(L)22, V_(L)23, V_(L)24,V_(L)25, V_(L)26, V_(L)27, V_(L)28, V_(L)29, V_(L)30, V_(L)31, V_(L)32,V_(L)33, V_(L)34, V_(L)35, V_(L)36, V_(L)37, V_(L)38, V_(L)39, V_(L)40,V_(L)41, V_(L)42, V_(L)43, V_(L)44, V_(L)45, V_(L)46, V_(L)47, V_(L)48,V_(L)49, V_(L)50, V_(L)51, V_(L)52, V_(L)53, V_(L)54, V_(L)55, V_(L)56,V_(L)57, V_(L)58, V_(L)59, V_(L)60, V_(L)61, V_(L)62, V_(L)63, V_(L)64,V_(L)65, V_(L)66, V_(L)67, V_(L)68, V_(L)69, V_(L)70, V_(L)71, V_(L)72,V_(L)73, V_(L)74, V_(L)75, V_(L)76, V_(L)77, V_(L)78, V_(L)79, V_(L)80,V_(L)81, V_(L)82, V_(L)83, V_(L)84, V_(L)85, V_(L)86, V_(L)87, V_(L)88,V_(L)89, V_(L)90, V_(L)91, V_(L)92, V_(L)93, V_(L)94, V_(L)95, V_(L)96,V_(L)97, V_(L)98, V_(L)99 and V_(L)100. Again another example of such anantigen binding protein comprises (a) one V_(L)3, and (b) one of V_(L)1,V_(L)2, V_(L)4, V_(L)5, V_(L)6, V_(L)7, V_(L)8, V_(L)9, V_(L)10,V_(L)11, V_(L)12, V_(L)13, V_(L)14, V_(L)15, V_(L)16, V_(L)17, V_(L)18,V_(L)19, V_(L)20, V_(L)21, V_(L)22, V_(L)23, V_(L)24, V_(L)25, V_(L)26,V_(L)27, V_(L)28, V_(L)29, V_(L)30, V_(L)31, V_(L)32, V_(L)33, V_(L)34,V_(L)35, V_(L)36, V_(L)37, V_(L)38, V_(L)39, V_(L)40, V_(L)41, V_(L)42,V_(L)43, V_(L)44, V_(L)45, V_(L)46, V_(L)47, V_(L)48, V_(L)49, V_(L)50,V_(L)51, V_(L)52, V_(L)53, V_(L)54, V_(L)55, V_(L)56, V_(L)57, V_(L)58,V_(L)59, V_(L)60, V_(L)61, V_(L)62, V_(L)63, V_(L)64, V_(L)65, V_(L)66,V_(L)67, V_(L)68, V_(L)69, V_(L)70, V_(L)71, V_(L)72, V_(L)73, V_(L)74,V_(L)75, V_(L)76, V_(L)77, V_(L)78, V_(L)79, V_(L)80, V_(L)81, V_(L)82,V_(L)83, V_(L)84, V_(L)85, V_(L)86, V_(L)87, V_(L)88, V_(L)89, V_(L)90,V_(L)91, V_(L)92, V_(L)93, V_(L)94, V_(L)95, V_(L)96, V_(L)97, V_(L)98,V_(L)99 and V_(L)100, etc.

The various combinations of heavy chain variable regions can be combinedwith any of the various combinations of light chain variable regions.

In other embodiments, an antigen binding protein comprises two identicallight chain variable regions and/or two identical heavy chain variableregions. As an example, the antigen binding protein can be an antibodyor immunologically functional fragment thereof that includes two lightchain variable regions and two heavy chain variable regions incombinations of pairs of light chain variable regions and pairs of heavychain variable regions as listed in Tables 2A and 2B.

Some antigen binding proteins that are provided comprise a heavy chainvariable domain comprising a sequence of amino acids that differs fromthe sequence of a heavy chain variable domain selected from V_(H)1,V_(H)2, V_(H)3, V_(H)4, V_(H)5, V_(H)6, V_(H)7, V_(H)8, V_(H)9, V_(H)10,V_(H)11, V_(H)12, V_(H)13, V_(H)14, V_(H)15, V_(H)16, V_(H)17, V_(H)18,V_(H)19, V_(H)20, V_(H)21 V_(H)22, V_(H)23, V_(H)24, V_(H)25, V_(H)26,V_(H)27, V_(H)28, V_(H)29, V_(H)30, V_(H)31, V_(H)32, V_(H)33, V_(H)34,V_(H)35, V_(H)36, V_(H)37, V_(H)38, V_(H)39, V_(H)40, V_(H)41, V_(H)42,V_(H)43, V_(H)44, V_(H)45, V_(H)46, V_(H)47, V_(H)48, V_(H)49, V_(H)50,V_(H)51, V_(H)52, V_(H)53, V_(H)54, V_(H)55, V_(H)56, V_(H)57, V_(H)58,V_(H)59, V_(H)60, V_(H)61, V_(H)62, V_(H)63, V_(H)64, V_(H)65, V_(H)66,V_(H)67, V_(H)68, V_(H)69, V_(H)70, V_(H)71, V_(H)72, V_(H)73, V_(H)74,V_(H)75, V_(H)76, V_(H)77, V_(H)78, V_(H)79, V_(H)80, 81, V_(H)82,V_(H)83, V_(H)84, V_(H)85, V_(H) 86, V_(H) 87, V_(H)88, V_(H)89,V_(H)90, V_(H)91, V_(H)92, V_(H)93, and V_(H)94 at only 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid residues, wherein eachsuch sequence difference is independently either a deletion, insertionor substitution of one amino acid, with the deletions, insertions and/orsubstitutions resulting in no more than 15 amino acid changes relativeto the foregoing variable domain sequences. The heavy chain variableregion in some antigen binding proteins comprises a sequence of aminoacids that has at least 70%, 75%, 80%, 85%, 90%, 95%, 97% or 99%sequence identity to the amino acid sequences of the heavy chainvariable region of V_(H)1, V_(H)2, V_(H)3, V_(H)4, V_(H)5, V_(H)6,V_(H)7, V_(H)8, V_(H)9, V_(H)10, V_(H)11, V_(H)12, V_(H)13, V_(H)14,V_(H)15, V_(H)16, V_(H)17, V_(H)18, V_(H)19, V_(H)20, V_(H)21 V_(H)22,V_(H)23, V_(H)24, V_(H)25, V_(H)26, V_(H)27, V_(H)28, V_(H)29, V_(H)30,V_(H)31, V_(H)32, V_(H)33, V_(H)34, V_(H)35, V_(H)36, V_(H)37, V_(H)38,V_(H)39, V_(H)40, V_(H)41, V_(H)42, V_(H)43, V_(H)44, V_(H)45, V_(H)46,V_(H)47, V_(H)48, V_(H)49, V_(H)50, V_(H)51, V_(H)52, V_(H)53, V_(H)54,V_(H)55, V_(H)56, V_(H)57, V_(H)58, V_(H)59, V_(H)60, V_(H)61, V_(H)62,V_(H)63, V_(H)64, V_(H)65, V_(H)66, V_(H)67, V_(H)68, V_(H)69, V_(H)70,V_(H)71, V_(H)72, V_(H)73, V_(H)74, V_(H)75, V_(H)76, V_(H)77, V_(H)78,V_(H)79, V_(H)80, 81, V_(H)82, V_(H)83, V_(H)84, V_(H)85, V_(H) 86,V_(H) 87, V_(H)88, V_(H)89, V_(H)90, V_(H)91, V_(H)92, V_(H)93, andV_(H)94.

Certain antigen binding proteins comprise a light chain variable domaincomprising a sequence of amino acids that differs from the sequence of alight chain variable domain selected from V_(L)1, V_(L)2, V_(L)3,V_(L)4, V_(L)5, V_(L)6, V_(L)7, V_(L)8, V_(L)9, V_(L)10, V_(L)11,V_(L)12, V_(L)13, V_(L)14, V_(L)15, V_(L)16, V_(L)17, V_(L)18, V_(L)19,V_(L)20, V_(L)21, V_(L)22, V_(L)23, V_(L)24, V_(L)25, V_(L)26, V_(L)27,V_(L)28, V_(L)29, V_(L)30, V_(L)31, V_(L)32, V_(L)33, V_(L)34, V_(L)35,V_(L)36, V_(L)37, V_(L)38, V_(L)39, V_(L)40, VAL V_(L)42, V_(L)43,V_(L)44, V_(L)45, V_(L)46, V_(L)47, V_(L)48, V_(L)49, V_(L)50, V_(L)51,V_(L)52, V_(L)53, V_(L)54, V_(L)55, V_(L)56, V_(L)57, V_(L)58, V_(L)59,V_(L)60, V_(L)61, V_(L)62, V_(L)63, V_(L)64, V_(L)65, V_(L)66, V_(L)67,V_(L)68, V_(L)69, V_(L)70, V_(L)71, V_(L)72, V_(L)73, V_(L)74, V_(L)75,V_(L)76, V_(L)77, V_(L)78, V_(L)79, V_(L)80, V_(L)81, V_(L)82, V_(L)83,V_(L)84, V_(L)85, V_(L)86, V_(L)87, V_(L)88, V_(L)89, V_(L)90, V_(L)91,V_(L)92, V_(L)93, V_(L)94, V_(L)95, V_(L)96, V_(L)97, V_(L)98, V_(L)99and V_(L)100 at only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15amino acid residues, wherein each such sequence difference isindependently either a deletion, insertion or substitution of one aminoacid, with the deletions, insertions and/or substitutions resulting inno more than 15 amino acid changes relative to the foregoing variabledomain sequences. The light chain variable region in some antigenbinding proteins comprises a sequence of amino acids that has at least70%, 75%, 80%, 85%, 90%, 95%, 97% or 99% sequence identity to the aminoacid sequences of the light chain variable region of V_(L)1, V_(L)2,V_(L)3, V_(L)4, V_(L)5, V_(L)6, V_(L)7, V_(L)8, V_(L)9, V_(L)10,V_(L)11, V_(L)12, V_(L)13, V_(L)14, V_(L)15, V_(L)16, V_(L)17, V_(L)18,V_(L)19, V_(L)20, V_(L)21, V_(L)22, V_(L)23, V_(L)24, V_(L)25, V_(L)26,V_(L)27, V_(L)28, V_(L)29, V_(L)30, V_(L)31, V_(L)32, V_(L)33, V_(L)34,V_(L)35, V_(L)36, V_(L)37, V_(L)38, V_(L)39, V_(L)40, V_(L)41, V_(L)42,V_(L)43, V_(L)44, V_(L)45, V_(L)46, V_(L)47, V_(L)48, V_(L)49, V_(L)50,V_(L)51, V_(L)52, V_(L)53, V_(L)54, V_(L)55, V_(L)56, V_(L)57, V_(L)58,V_(L)59, V_(L)60, V_(L)61, V_(L)62, V_(L)63, V_(L)64, V_(L)65, V_(L)66,V_(L)67, V_(L)68, V_(L)69, V_(L)70, V_(L)71, V_(L)72, V_(L)73, V_(L)74,V_(L)75, V_(L)76, V_(L)77, V_(L)78, V_(L)79, V_(L)80, V_(L)81, V_(L)82,V_(L)83, V_(L)84, V_(L)85, V_(L)86, V_(L)87, V_(L)88, V_(L)89, V_(L)90,V_(L)91, V_(L)92, V_(L)93, V_(L)94, V_(L)95, V_(L)96, V_(L)97, V_(L)98,V_(L)99 and V_(L)100.

In additional instances, antigen binding proteins comprise the followingpairings of light chain and heavy chain variable domains: V_(L)1 withV_(H)1, V_(L)2 with V_(H)1, V_(L)3 with V_(H)2 or V_(H)3, V_(L)4 withV_(H)4, V_(L)5 with V_(H)5, V_(L)6 with V_(H)6, V_(L)7 with V_(H)6,V_(L)8 with V_(H)7 or V_(H)8, V_(L)9 with V_(H)9, V_(L)10 with V_(H)9,V_(L)11 with V_(H) 10, V_(L)12 with V_(H)11, V_(L)13 with V_(H)12,V_(L)13 with V_(H)14, V_(L)14 with V_(H)13, V_(L)15 with V_(H)14,V_(L)16 with V_(H)15, V_(L)17 with V_(H)16, V_(L)18 with V_(H)17,V_(L)19 with V_(H)18, V_(L)20 with V_(H)19, V_(L)21 with V_(H)20,V_(L)22 with V_(H)21, V_(L)23 with V_(H)22, V_(L)24 with V_(H)23,V_(L)25 with V_(H)24, V_(L)26 with V_(H)25, V_(L)27 with V_(H)26,V_(L)28 with V_(H)27, V_(L)29 with V_(H)28, V_(L)30 with V_(H)29,V_(L)31 with V_(H)30, V_(L)32 with V_(H)31, V_(L)33 with V_(H)32,V_(L)34 with V_(H)33, V_(L)35 with V_(H)34, V_(L)36 with V_(H)35,V_(L)37 with V_(H)36, V_(L)38 with V_(H)37, V_(L)39 with V_(H)38,V_(L)40 with V_(H)39, V_(L)41 with V_(H)40, V_(L)42 with V_(H)41,V_(L)43 with V_(H)42, V_(L)44 with V_(H)43, V_(L)45 with V_(H)44,V_(L)46 with V_(H)45, V_(L)47 with V_(H)46, V_(L)48 with V_(H)47,V_(L)49 with V_(H)48, V_(L)50 with V_(H)49, V_(L)51 with V_(H)50, 52with V_(H)51, V_(L)53 with V_(H)52, V_(L)54 with V_(H)53, V_(L)55 with54, and V_(L)56 with V_(H)54, V_(L)57 with V_(H)54, V_(L)58 withV_(H)55, V_(L)59 with V_(H)56, V_(L)60 with V_(H)57, V_(L)61 withV_(H)58, V_(L)62 with V_(H)59, V_(L)63 with V_(H)60, V_(L)64 withV_(H)1, V_(L)65 with V_(H)62, V_(L)66 with V_(H)63, V_(L)67 withV_(H)64, V_(L)68 with V_(H)65, V_(L)69 with V_(H)66, V_(L)70 withV_(H)67, V_(L)71 with V_(H)68, V_(L)72 with V_(H)69, V_(L)73 withV_(H)70, V_(L)74 with V_(H)70, and V_(L)75 with V_(H)70, V_(L)76 withV_(H)71, V_(L)77 with V_(H)72, V_(L)78 with V_(H)73, V_(L)79 withV_(H)74, V_(L)80 with V_(H)75, V_(L)81 with V_(H)76, V_(L)82 withV_(H)77, V_(L)83 with V_(H)78, V_(L)84 with V_(H)79, V_(L)85 withV_(H)80, V_(L)86 with V_(H)81, V_(L)87 with V_(H)82, V_(L)88 withV_(H)86, V_(L)89 with V_(H)83, V_(L)90 with V_(H)84, V_(L)91 withV_(H)85, V_(L) 92 with V_(H) 87, V_(L) 93 with V_(H) 88, V_(L) 94 withV_(H) 88, V_(L) 95 with V_(H) 89, V_(L) 96 with V_(H) 90, V_(L) 97 withV_(H) 91, V_(L) 98 with V_(H) 92, V_(L) 99 with V_(H) 93, and V_(L) 100with V_(H) 94.

In some instances, the antigen binding proteins in the above pairingscan comprise amino acid sequences that have 70%, 75%, 80%, 85%, 90%,95%, 96%, 97%, 98% or 99% sequence identity with the specified variabledomains.

Still other antigen binding proteins, e.g., antibodies orimmunologically functional fragments, include variant forms of a variantheavy chain and a variant light chain as just described.

Antigen Binding Protein CDRs

In various embodiments, the antigen binding proteins disclosed hereincan comprise polypeptides into which one or more CDRs are grafted,inserted and/or joined. An antigen binding protein can have 1, 2, 3, 4,5 or 6 CDRs. An antigen binding protein thus can have, for example, oneheavy chain CDR1 (“CDRH1”), and/or one heavy chain CDR2 (“CDRH2”),and/or one heavy chain CDR3 (“CDRH3”), and/or one light chain CDR1(“CDRL1”), and/or one light chain CDR2 (“CDRL2”), and/or one light chainCDR3 (“CDRL3”). Some antigen binding proteins include both a CDRH3 and aCDRL3. Specific heavy and light chain CDRs are identified in Tables 3Aand 3B, respectively, infra.

Complementarity determining regions (CDRs) and framework regions (FR) ofa given antibody can be identified using the system described by Kabatet al., (1991) “Sequences of Proteins of Immunological Interest”, 5thEd., US Dept. of Health and Human Services, PHS, NIH, NIH Publicationno. 91-3242. Although presented in the Kabat nomenclature scheme, asdesired, the CDRs disclosed herein can also be redefined according analternative nomenclature scheme, such as that of Chothia (see Chothia &Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature342:878-883 or Honegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670).Certain antibodies that are disclosed herein comprise one or more aminoacid sequences that are identical or have substantial sequence identityto the amino acid sequences of one or more of the CDRs presented inTable 3A (CDRHs) and Table 3B (CDRLs), infra.

TABLE 3A Exemplary CDRH Sequences Con- tained SEQ in ID Refer- Designa-Clone NO: ence tion Sequence 48C9 603 V_(H)73 CDRH1-1 GYYWT 49A12V_(H)73 51E2 V_(H)73 48F3 604 V_(H)72 CDRH1-2 GYYWS 51E5 V_(H)74 52C5V_(H)70 55E4 V_(H)70 60G5.1 V_(H)70 49B11 V_(H)70 50H10 V_(H)70 53C1V_(H)70 56G1 V_(H)71 51C1 V_(H)89 48F8 605 V_(H)48 CDRH1-3 SYSMN 51G2V_(H)50 56A7 V_(H)51 53B9 V_(H)48 56B4 V_(H)48 57E7 V_(H)48 57F11V_(H)48 56E4 V_(H)51 55E6 V_(H)93 48H11 606 V_(H)39 CDRH1-4 GYYKH 48G4607 V_(H)83 CDRH1-5 ELSIH 53C3.1 V_(H)83 49A10 608 V_(H)62 CDRH1-6 NYGMH58C2 V_(H)85 59G10.2 V_(H)57 48D4 V_(H)62 49C8 609 V_(H)44 CDRH1-7 SYDID52H1 V_(H)44 49G2 610 V_(H)63 CDRH1-8 NYGMR 50C12 V_(H)63 55G11 V_(H)6349G3 611 V_(H)46 CDRH1-9 NPRMGVS 49H12 612 V_(H)42 CDRH1-10 SYDIN 54A1V_(H)43 55G9 V_(H)43 50G1 613 V_(H)84 CDRH1-11 SYGLH 51A8 614 V_(H)58CDRH1-12 SYGMH 52C1 V_(H)64 53H5.2 V_(H)59 56C11 V_(H)61 60D7 V_(H)6664H5 V_(H)7 65G4 V_(H)8 66G2 V_(H)11 68G5 V_(H)12 64C8 V_(H)23 67G8V_(H)27 68D3v2 51C10.1 615 V_(H)54 CDRH1-13 NYAMS 59D10v1 V_(H)5459D10v2 V_(H)54 51C10.2 616 V_(H)67 CDRH1-14 SGGYYWS 64A6 V_(H)29 52A8617 V_(H)40 CDRH1-15 GYYLH 66B4 V_(H)10 52B8 618 V_(H)77 CDRH1-16 YYYWS52F8 619 V_(H)41 CDRH1-17 GYYTH 52H2 620 V_(H)79 CDRH1-18 TYYWS 53F6 621V_(H)60 CDRH1-19 TYGMH 53H5.3 622 V_(H)75 CDRH1-20 DYYWN 54H10.1 623V_(H)52 CDRH1-21 SYAMS 60F9 V_(H)55 61G5 V_(H)56 55D1 V_(H)52 48H3V_(H)52 53C11 V_(H)52 48B4 V_(H)55 52D6 V_(H)55 55D3 624 V_(H)68CDRH1-22 SGVYYWN 55E9 625 V_(H)65 CDRH1-23 SFGMH 55G5 626 V_(H)78CDRH1-24 SYYWS 65C3 V_(H)5 68D5 V_(H)5 67F5 V_(H)31 55A7 V_(H)92 56E7627 V_(H)81 CDRH1-25 SYWIG 67A5 V_(H)34 67C10 V_(H)35 64H6 V_(H)3656G3.2 628 V_(H)80 CDRH1-26 SYYWN 56G3.3 629 V_(H)76 CDRH1-27 SSSYYWG55B10 V_(H)76 61H5 V_(H)86 52B9 V_(H)86 57B12 630 V_(H)69 CDRH1-28SGVYYWS 57D9 631 V_(H)82 CDRH1-29 SNSATWN 59A10 632 V_(H)47 CDRH1-30DSYMS 49H4 V_(H)47 59C9 633 V_(H)49 CDRH1-31 SYSMS 58A5 V_(H)49 57A4V_(H)49 57F9 V_(H)49 59G10.3 634 V_(H)53 CDRH1-32 HYAMS 60G5.2 635V_(H)45 CDRH1-33 NYGIS 63G8 636 V_(H)1 CDRH1-34 SYGIH 64A8 V_(H)1 67B4V_(H)1 68D3 V_(H)1 64E6 637 V_(H)2 CDRH1-35 SGDYYWT 65E8 V_(H)2 65F11V_(H)2 67G7 V_(H)2 63H11 V_(H)3 63F5 V_(H)13 65C1 V_(H)15 66F6 V_(H)1463B6 638 V_(H)4 CDRH1-36 SGDYYWS 64D4 V_(H)4 65F9 V_(H)30 64B10 V_(H)3264B10v2 63E6 639 V_(H)6 CDRH1-37 GYYMH 66F7 V_(H)6 50G5 v1 V_(H)88 50G5v2 V_(H)88 67G10v1 640 V_(H)9 CDRH1-38 NAWMS 67G10v2 V_(H)9V_(H)21 63A10V_(H)22 65H11 53C3.2 641 V_(H)90 CDRH1-39 SGNYYWS 64A7 642 V_(H)16CDRH1-40 SDTSYWG 50D4 643 V_(H)87 CDRH1-41 SHDIN 61E1 644 V_(H)94CDRH1-42 SNSAAWN 66D4 645 V_(H)17 CDRH1-43 GYYIH 54H10.3 V_(H)91 65B1646 V_(H)18 CDRH1-44 GYFMH 67A4 647 V_(H)19 CDRH1-45 TYDMH 65B4 648V_(H)20 CDRH1-46 SYDMH 65E3 649 V_(H)24 CDRH1-47 NYNMH 65D4 650 V_(H)25CDRH1-48 FYGMH 65D1 651 V_(H)26 CDRH1-49 YYYIH 65B7 652 V_(H)28 CDRH1-50SDAYYWS 68C8 653 V_(H)33 CDRH1-51 SGDNYWS 63F9 654 V_(H)37 CDRH1-52SGGYYWN 67F6v1 655 V_(H)38 CDRH1-53 GYWIG 67F6v2 V_(H)38 48C9 656V_(H)73 CDRH2-1 EINHSENTNYNPSLKS 52C5 V_(H)70 55E4 V_(H)70 56G1 V_(H)7149A12 V_(H)73 51E2 V_(H)73 60G5.1 V_(H)70 49B11 V_(H)70 50H10 V_(H)7053C1 V_(H)70 51C1 V_(H)89 48F3 657 V_(H)72 CDRH2-2 EITHTGSSNYNPSLKS 48F8658 V_(H)48 CDRH2-3 SISSSSSYEYYVDSVKG 53B9 V_(H)48 56B4 V_(H)48 57E7V_(H)48 57F11 V_(H)48 48H11 659 V_(H)39 CDRH2-4 WINPNSGATKYAQKFQG 48G4660 V_(H)83 CDRH2-5 GFDPEDGETIYAQKFQG 53C3.1 V_(H)83 49A10 661 V_(H)62CDRH2-6 IIWYDGSNKNYADSVKG 48D4 V_(H)62 49C8 662 V_(H)44 CDRH2-7WMNPNGGNTGYAQKFQG 52H1 V_(H)44 49G2 663 V_(H)63 CDRH2-8LIWYDGSNKFYADSVKG 50C12 V_(H)63 55G11 V_(H)63 49G3 664 V_(H)46 CDRH2-9HIFSNDEKSYSTSLKS 49H12 665 V_(H)42 CDRH2-10 WMNPYSGSTGYAQNFQG 50G1 666V_(H)84 CDRH2-11 VIWNDGSNKLYADSVKG 51A8 667 V_(H)58 CDRH2-12VISYDGSNKYYADSVKG 63G8 V_(H)1 64A8 V_(H)1 67B4 V_(H)1 68D3 V_(H)151C10.1 668 V_(H)54 CDRH2-13 GISGSSAGTYYADSVKG 59D10v1 V_(H)54 59D10v2V_(H)54 51C10.2 669 V_(H)67 CDRH2-14 YIYYNGSPYDNPSLKR 51E5 670 V_(H)74CDRH2-15 ELDHSGSINYNPSLKS 51G2 671 V_(H)50 CDRH2-16 SISSSSTYIYYADSVKG56A7 V_(H)51 56E4 V_(H)51 52A8 672 V_(H)40 CDRH2-17 WINPNSAATNYAPKFQG52B8 673 V_(H)77 CDRH2-18 YIYYSGSTNYNPSLKS 55A7 V_(H)92 52C1 674 V_(H)64CDRH2-19 VIWYDGSNNYYADSVKG 52F8 675 V_(H)41 CDRH2-20 WINPSSGDTKYAQKFQG52H2 676 V_(H)79 CDRH2-21 YIFYNGNANYSPSLKS 53F6 677 V_(H)60 CDRH2-22VIWYDGSNKYYADSVKG 60D7 V_(H)66 65D4 V_(H)25 53H5.2 678 V_(H)59 CDRH2-23LISYDGSNKYYADSVKG 53H5.3 679 V_(H)75 CDRH2-24 EINHSGTTNYNPSLKS 54A1 680V_(H)43 CDRH2-25 WMNPHSGNTGYAQKFQG 55G9 V_(H)43 54H10.1 681 V_(H)52CDRH2-26 AISGSGRTTYSADSVKG 55D1 V_(H)52 48H3 V_(H)52 53C11 V_(H)52 55D3682 V_(H)68 CDRH2-27 YLYYSGSTYYNPSLKS 55E9 683 V_(H)65 CDRH2-28LIWYDGDNKYYADSVKG 55G5 684 V_(H)78 CDRH2-29 RIYISGSTNYNPSLEN 56C11 685V_(H)61 CDRH2-30 VIWYDGSYQFYADSVKG 56E7 686 V_(H)81 CDRH2-31IIYPGDSDTRYSPSFQG 67A5 V_(H)34 67C10 V_(H)35 67F6v1 V_(H)38 67F6v2V_(H)38 56G3.2 687 V_(H)80 CDRH2-32 RIYTSGSTNYNPSLKS 56G3.3 688 V_(H)76CDRH2-33 MIYYSGTTYYNPSLKS 55B10 V_(H)76 56G3.3 V_(H)76 57B12 689 V_(H)69CDRH2-34 YIYYSGSTYYNPSLKS 63H11 V_(H)3 66F6 V_(H)14 65F9 V_(H)30 57D9690 V_(H)82 CDRH2-35 RTYYRSKWYNDYAVSVKS 61E1 V_(H)94 58C2 691 V_(H)85CDRH2-36 VIWNDGNNKYYADSVKG 59A10 692 V_(H)47 CDRH2-37 SISSSGSIVYFADSVKG49H4 V_(H)47 59C9 693 V_(H)49 CDRH2-38 SISSSSTYIYYADSLKG 58A5 V_(H)4957A4 V_(H)49 57F9 V_(H)49 59G10.2 694 V_(H)57 CDRH2-39 ITSYGGSNKNYADSVKG59G10.3 695 V_(H)53 CDRH2-40 AISGSGAGTFYADSMKG 60F9 696 V_(H)55 CDRH2-41VISDSGGSTYYADSVKG 48B4 V_(H)55 52D6 V_(H)55 60G5.2 697 V_(H)45 CDRH2-42WISAYNGYSNYAQKFQD 61G5 698 V_(H)56 CDRH2-43 VISGSGGDTYYADSVKG 64E6 699V_(H)2 CDRH2-44 YIYYTGSTYYNPSLKS 65E8 V_(H)2 65F11 V_(H)2 67G7 V_(H)263B6 700 V_(H)4 CDRH2-45 YIYYSGTTYYNPSLKS 64D4 V_(H)4 65C3 701 V_(H)5CDRH2-46 YIYYTGSTNYNPSLKS 68D5 V_(H)5 63E6 702 V_(H)6 CDRH2-47WMNPNSGATKYAQKFQG 66F7 V_(H)6 64H5 703 V_(H)7 CDRH2-48 VIWDDGSNKYYADSVKG65G4 V_(H)8 67G10v1 704 V_(H)9 CDRH2-49 RIKSKTDGGTTEYAAPVKG 67G10v2V_(H)9 63F5 705 V_(H)13 CDRH2-50 YIYYSGSAYYNPSLKS 64A7 706 V_(H)16CDRH2-51 NIYYSGTTYFNPSLKS 65C1 707 V_(H)15 CDRH2-52 YIFYSGSTYYNPSLKS65B7 V_(H)28 66B4 708 V_(H)10 CDRH2-53 WINPNSGGTDYAQKFQG 66G2 709V_(H)11 CDRH2-54 GISYDGSNKNYADSVKG 68G5 710 V_(H)12 CDRH2-55VIWYDGSNKYHADSVKG 66D4 711 V_(H)17 CDRH2-56 WINPPSGATNYAQKFRG 65B1 712V_(H)18 CDRH2-57 WINPNSGATNYAQKFHG 67A4 713 V_(H)19 CDRH2-58AIGIAGDTYYSDSVKG 65B4 714 V_(H)20 CDRH2-59 TIDTAGDAYYPGSVKG 63A10 715V_(H)21 CDRH2-60 RIKSKTDGGTTDYAAPVKG 67G10v1 67G10v2 65H11 716 V_(H)22CDRH2-61 RIIGKTDGGTTDYAAPVKG 64C8 717 V_(H)23 CDRH2-62 VISYDGSNKHYADSVKG65E3 718 V_(H)24 CDRH2-63 VLWYDGNTKYYADSVKG 65D1 719 V_(H)26 CDRH2-64LIWYDGSNKDYADSVKG 67G8 720 V_(H)27 CDRH2-65 VIWYDGSNKDYADSVKG 64A6 721V_(H)29 CDRH2-66 YIYYSGGTHYNPSLKS 67F5 722 V_(H)31 CDRH2-67YIYYSGNTNYNPSLKS 64B10 723 V_(H)32 CDRH2-68 FIYYSGGTNYNPSLKS 68C8 724V_(H)33 CDRH2-69 FMFYSGSTNYNPSLKS 64H6 725 V_(H)36 CDRH2-70IIYPGDSETRYSPSFQG 63F9 726 V_(H)37 CDRH2-71 YIYDSGSTYYNPSLKS 61H5 727V_(H)86 CDRH2-72 SIYYSGTTYYNPSLKS 52B9 V_(H)86 50G5v1 728 V_(H)88CDRH2-73 WINPDSGGTNYAQKFQG 50G5v2 V_(H)88 54H10.3 729 V_(H)91 CDRH2-74WINPNSGGTNYAQKFRG 50D4 730 V_(H)87 CDRH2-75 WMNPYSGSTGLAQRFQD 55E6 731V_(H)93 CDRH2-76 YISSGSSTIYHADSVKG 53C3.2 732 V_(H)90 CDRH2-77YIYHSGSAYYNPSLKS 64B10v2 1868 V_(H)96 CDRH2-78 FIYYSGGTNYNPPLKS 68D3v21869 V_(H)95 CDRH2-79 FISYAGSNKYYADSVKG 48C9 733 V_(H)73 CDRH3-1ESGNFPFDY 49A12 V_(H)73 51E2 V_(H)73 48F3 734 V_(H)72 CDRH3-2GGILWFGEQAFDI 48F8 735 V_(H)48 CDRH3-3 SLSIAVAASDY 53B9 V_(H)48 56B4V_(H)48 57E7 V_(H)48 57F11 V_(H)48 48H11 736 V_(H)39 CDRH3-4EVPDGIVVAGSNAFDF 48G4 737 V_(H)83 CDRH3-5 HSGSGRFYYYYYGMDV 53C3.1V_(H)83 49A10 738 V_(H)62 CDRH3-6 DQDYDFWSGYPYFYYYGMDV 48D4 V_(H)62 49C8739 V_(H)44 CDRH3-7 GKEFSRAEFDY 52H1 V_(H)44 49G2 740 V_(H)63 CDRH3-8DRYYDFWSGYPYFFYYGLDV 50C12 V_(H)63 55G11 V_(H)63 49G3 741 V_(H)46CDRH3-9 VDTLNYHYYGMDV 49H12 742 V_(H)42 CDRH3-10 YNWNYGAFDF 54A1 V_(H)4355G9 V_(H)43 50G1 743 V_(H)84 CDRH3-11 DQYYDFWSGYPYYHYYGMDV 51A8 744V_(H)58 CDRH3-12 ADGDYPYYYYYYGMDV 51C10.1 745 V_(H)54 CDRH3-13DWSIAVAGTFDY 59D10v1 V_(H)54 59D10v2 V_(H)54 51C10.2 746 V_(H)67CDRH3-14 GALYGMDV 51E5 747 V_(H)74 CDRH3-15 VLGSTLDY 51G2 748 V_(H)50CDRH3-16 DTYISGWNYGMDV 52A8 749 V_(H)40 CDRH3-17 EGGTYNWFDP 52B8 750V_(H)77 CDRH3-18 GTRAFDI 52C1 751 V_(H)64 CDRH3-19 DRAGASPGMDV 52C5 752V_(H)70 CDRH3-20 VTGTDAFDF 60G5.1 V_(H)70 49B11 V_(H)70 50H10 V_(H)7053C1 V_(H)70 51C1 V_(H)89 55E4 V_(H)70 56G1 V_(H)71 52F8 753 V_(H)41CDRH3-21 SGWYPSYYYGMDV 52H2 754 V_(H)79 CDRH3-22 ETDYGDYARPFEY 53F6 755V_(H)60 CDRH3-23 GHYDSSGPRDY 53H5.2 756 V_(H)59 CDRH3-24 EANWGYNYYGMDV53H5.3 757 V_(H)75 CDRH3-25 ILRYFDWLEYYFDY 61E1 758 V_(H)94 CDRH3-26EGSWSSFFDY 54H10 759 V_(H)52 CDRH3-27 EQQWLVYFDY 55D1 V_(H)52 48H3V_(H)52 53C11 V_(H)52 55D3 760 V_(H)68 CDRH3-28 DGITMVRGVTHYYGMDV 57B12V_(H)69 55E6 761 V_(H)93 CDRH3-29 EGYYDSSGYYYNGMDV 55E9 762 V_(H)65CDRH3-30 NSGWDYFYYYGMDV 55G5 763 V_(H)78 CDRH3-31 SGSYSFDY 56A7 764V_(H)51 CDRH3-32 DIYSSGWSYGMDV 56E4 V_(H)51 56C11 765 V_(H)61 CDRH3-33DHVWRTYRYIFDY 56E7 766 V_(H)81 CDRH3-34 AQLGIFDY 50G5v1 767 V_(H)88CDRH3-35 GGYSYGYEDYYGMDV 50G5v2 V_(H)88 56G3.2 768 V_(H)80 CDRH3-36GPLWFDY 56G3.3 769 V_(H)76 CDRH3-37 VAAVYWYFDL 55B10 V_(H)76 61H5V_(H)86 52B9 V_(H)86 55A7 770 V_(H)92 CDRH3-38 GITGTIDF 57D9 771 V_(H)82CDRH3-39 IVVVPAVLFDY 58C2 772 V_(H)85 CDRH3-40 DQNYDFWNGYPYYFYYGMDV59A10 773 V_(H)47 CDRH3-41 ETFSSGWFDAFDI 49H4 V_(H)47 59C9 774 V_(H)49CDRH3-42 DRWSSGWNEGFDY 58A5 V_(H)49 57A4 V_(H)49 57F9 V_(H)49 53C3.2 775V_(H)90 CDRH3-43 TTGASDI 59G10.2 776 V_(H)57 CDRH3-44 EAGYSFDY 59G10.3777 V_(H)53 CDRH3-45 DLRIAVAGSFDY 60D7 778 V_(H)66 CDRH3-46DQYFDFWSGYPFFYYYGMDV 60F9 779 V_(H)55 CDRH3-47 DHSSGWYYYGMDV 48B4V_(H)55 52D6 V_(H)55 60G5.2 780 V_(H)45 CDRH3-48 EEKQLVKDYYYYGMDV 61G5781 V_(H)56 CDRH3-49 DHTSGWYYYGMDV 63G8 782 V_(H)1 CDRH3-50TVTKEDYYYYGMDV 64A8 V_(H)1 67B4 V_(H)1 68D3 V_(H)1 66G2 V_(H)11 64E6 783V_(H)2 CDRH3-51 MTTPYWYFDL 65E8 V_(H)2 65F11 V_(H)2 67G7 V_(H)2 63H11V_(H)3 63F5 V_(H)13 66F6 V_(H)14 63B6 784 V_(H)4 CDRH3-52 MTTPYWYFGL64D4 V_(H)4 65C3 785 V_(H)5 CDRH3-53 EYYYGSGSYYP 68D5 V_(H)5 67F5V_(H)31 63E6 786 V_(H)6 CDRH3-54 ELGDYPFFDY 66F7 V_(H)6 64H5 787 V_(H)7CDRH3-55 EYVAEAGFDY 65G4 V_(H)8 67G10v1 788 V_(H)9 CDRH3-56DSSGSYYVEDYFDY 67G10 v2 V_(H)9 63A10 V_(H)21 65H11 V_(H)22 64A7 789V_(H)16 CDRH3-57 LRGVYWYFDL 65C1 790 V_(H)15 CDRH3-58 MTSPYWYFDL 66B4791 V_(H)10 CDRH3-59 DAATGRYYFDN 68G5 792 V_(H)12 CDRH3-60 DPGYSYGHFDY66D4 793 V_(H)17 CDRH3-61 ETGTWSFFDY 65B1 794 V_(H)18 CDRH3-62ELGIFNWFDP 67A4 795 V_(H)19 CDRH3-63 DRSSGRFGDYYGMDV 65B4 796 V_(H)20CDRH3-64 DRSSGRFGDFYGMDV 64C8 797 V_(H)23 CDRH3-65 ELLWFGEYGVDHGMDV 65E3798 V_(H)24 CDRH3-66 DVYGDYFAY 65D4 799 V_(H)25 CDRH3-67 ALNWNFFDY 65D1800 V_(H)26 CDRH3-68 EGTTRRGFDY 67G8 801 V_(H)27 CDRH3-69 SAVALYNWFDP65B7 802 V_(H)28 CDRH3-70 ESRILYFNGYFQH 64A6 803 V_(H)29 CDRH3-71VLHYSDSRGYSYYSDF 65F9 804 V_(H)30 CDRH3-72 VLHYYDSSGYSYYFDY 64B10v1 805V_(H)32 CDRH3-73 YSSTWDYYYGVDV 64B10v2 V_(H)32 68C8 806 V_(H)33 CDRH3-74YRSDWDYYYGMDV 67A5 807 V_(H)34 CDRH3-75 RASRGYRFGLAFAI 67C10 808 V_(H)35CDRH3-76 RASRGYRYGLAFAI 64H6 809 V_(H)36 CDRH3-77 VAVSAFNWFDP 63F9 810V_(H)37 CDRH3-78 DVLMVYTKGGYYYYGVDV 67F6v1 811 V_(H)38 CDRH3-79RASRGYSYGHAFDF 67F6v2 V_(H)38 50D4 812 V_(H)87 CDRH3-80 DLSSGYYYYGLDV54H10.3 813 V_(H)91 CDRH3-81 EEDYSDHHYFDY 66D4 1870 V_(H)17 CDRH3-82ETGTWNFFDY 68D3v2 1871 V_(H)95 CDRH3-83 TVTEEDYYYYGMDV

TABLE 3B Exemplary CDRL Sequences SEQ Contained ID in Desig- Amino AcidClone NO: Reference nation Sequence 48C9 814 V_(L)78 CDRL1-1 RASQNIRTYLN49A12 V_(L)78 51E2 V_(L)78 48F3 815 V_(L)77 CDRL1-2 RASQRISSYLN 48F8 816V_(L)49 CDRL1-3 RASQDIGNSLH 53B9 V_(L)49 56B4 V_(L)49 57E7 V_(L)49 57F11V_(L)49 48H11 817 V_(L)40 CDRL1-4 RASQNIRSYLN 49A10 818 V_(L)65 CDRL1-5RSSQSLLDSDDGNTYLD 48D4 V_(L)65 49C8 819 V_(L)45 CDRL1-6 QASQDINIYLN 52H1V_(L)45 49G2 820 V_(L)66 CDRL1-7 RSSQSLLDSDDGDTYLD 50C12 V_(L)66 55G11V_(L)66 60D7 V_(L)69 50G1 V_(L)90 49G3 821 V_(L)47 CDRL1-8 QASQGISNYLN49H12 822 V_(L)43 CDRL1-9 QASQDITKYLN 51A8 823 V_(L)61 CDRL1-10TRSSGSIASDYVQ 51C10.1 824 V_(L)55 CDRL1-11 SGDALPKKYAY 51C10.2 825V_(L)70 CDRL1-12 SGDELGDKYAC 51E5 826 V_(L)79 CDRL1-13 RASQDIRNDLG63G8v1 V_(L)104 64A8 V_(L)1 67B4 V_(L)1 68D3 V_(L)2 51G2 827 V_(L)51CDRL1-14 RASQGISSWLA 59A10 V_(L)48 49H4 V_(L)48 52A8 828 V_(L)41CDRL1-15 RASQTISSYLN 52B8 829 V_(L)82 CDRL1-16 RASQSVSDILA 52C1 830V_(L)67 CDRL1-17 SGSSSNIGINYVS 52C5 831 V_(L)73 CDRL1-18 RASQSISNYLN55E4 V_(L)75 49B11 V_(L)75 50H10 V_(L)75 53C1 V_(L)75 56G1 V_(L)76 51C1V_(L)95 60G5.1 V_(L)74 52F8 832 V_(L)42 CDRL1-19 RSSQSLLHSNGYNYLD 52H2833 V_(L)84 CDRL1-20 RASQSVRSSYLA 53F6 834 V_(L)63 CDRL1-21RSSQSLQHSNGYNYLD 53H5.2 835 V_(L)62 CDRL1-22 RASQGIRNDLG 50G5 v1 V_(L)9366G2 V_(L)12 53H5.3 836 V_(L)80 CDRL1-23 RASQSVSSNVA 54A1 837 V_(L)44CDRL1-24 QASQDISIYLN 55G9 V_(L)44 54H10.1 838 V_(L)53 CDRL1-25RASQSFSSSYLA 55D1 V_(L)53 48H3 V_(L)53 53C11 V_(L)53 55D3 839 V_(L)71CDRL1-26 RASQDISNYLA 50D4 V_(L)92 55E9 840 V_(L)68 CDRL1-27RSSQSLLHSNGFNYLD 55G5 841 V_(L)83 CDRL1-28 SGDNLGDKYAF 56A7 842 V_(L)52CDRL1-29 RASQDISSWLA 56E4 V_(L)52 56C11 843 V_(L)64 CDRL1-30 GGNDIGSKSVH56E7 844 V_(L)86 CDRL1-31 QASQDIKKFLN 56G3.2 845 V_(L)85 CDRL1-32RARQSVGSNLI 56G3.3 846 V_(L)81 CDRL1-33 RASQSVSRDYLA 55B10 V_(L)81 61H5V_(L)88 52B9 V_(L)88 57B12 847 V_(L)72 CDRL1-34 RASHDISNYLA 57D9 848V_(L)87 CDRL1-35 RASPSVSSSYLA 53C3.2 849 V_(L)96 CDRL1-36 RASQSISSNLA59C9 850 V_(L)50 CDRL1-37 RASQDIDSWLV 58A5 V_(L)50 57A4 V_(L)50 57F9V_(L)50 59D10 v1 851 V_(L)56 CDRL1-38 SGDAVPKKYAN 59D10 v2 852 V_(L)57CDRL1-39 SGDKLGDKYVC 65D1 V_(L)27 59G10.2 853 V_(L)60 CDRL1-40SGDNLGDKYAC 59G10.3 854 V_(L)54 CDRL1-41 SGSSSNIGDNYVS 54H10.3 855V_(L)97 CDRL1-84 RASQTISIYLN 60F9 856 V_(L)58 CDRL1-43 RASQRVPSSYIV 48B4V_(L)58 52D6 V_(L)58 60G5.2 857 V_(L)46 CDRL1-44 SGNKLGDKYVC 61G5 858V_(L)59 CDRL1-45 RASQRVPSSYLV 64E6 859 V_(L)3 CDRL1-46 RASQSVRNSYLA 65E8V_(L)3 65F11 V_(L)3 67G7 V_(L)3 63H11 V_(L)3 66F6 V_(L)15 63B6 860V_(L)4 CDRL1-47 RASQSVSNSYLA 64D4 V_(L)4 65C3 861 V_(L)5 CDRL1-48RASQSVSSQLA 68D5 V_(L)5 63E6 862 V_(L)6 CDRL1-49 RTSQSISSYLN 66F7 863V_(L)7 CDRL1-50 RTSQSISNYLN 64H5 864 V_(L)8 CDRL1-51 GGNNIGSKNVH 65G4V_(L)8 65E3 V_(L)25 64H6 V_(L)37 67G10 v1 865 V_(L)9 CDRL1-52GGNNIGSKAVH 63A10 v1 V_(L)22 63A10v2 V_(L)101 67G10 v2 866 V_(L)10CDRL1-53 SGDKLGDKYAC 63F5 867 V_(L)14 CDRL1-54 RASQTVRNNYLA 64A7 868V_(L)17 CDRL1-55 RASQSVSRNYLA 65C1 869 V_(L)16 CDRL1-56 RASQTIRNSYLA66B4 870 V_(L)11 CDRL1-57 RASQGISRWLA 55A7 871 V_(L)98 CDRL1-58RASQSISSYLN 68G5 872 V_(L)13 CDRL1-59 GGNNIGSINVH 66D4 873 V_(L)18CDRL1-60 RASQIISRYLN 65B1 874 V_(L)19 CDRL1-61 RASQNINNYLN 67A4 875V_(L)20 CDRL1-62 GGNNIGSKSVH 65B4 876 V_(L)21 CDRL1-63 GGNNIGSKSVQ 55E6877 V_(L)99 CDRL1-64 RASQSVSRSHLA 65H11 878 V_(L)23 CDRL1-65 GGNNIGSKTVH64C8 879 V_(L)24 CDRL1-66 RSSPSLVYSDGNTYLN 65D4 880 V_(L)26 CDRL1-67GGNDIGSKNVH 61E1 881 V_(L)100 CDRL1-68 RASQSIGTFLN 67G8 882 V_(L)28CDRL1-69 GGNNIGSYNVF 65B7 883 V_(L)29 CDRL1-70 RASQSVSSMYLA 64A6 884V_(L)30 CDRL1-71 RASQSVNSNLA 65F9 885 V_(L)31 CDRL1-72 RASQSVSSNLA 67F5V_(L)32 64B10 886 V_(L)33 CDRL1-73 SGSSSNIGNNYVA 68C8 887 V_(L)34CDRL1-74 SGSSSNIGNNYVS 67A5 888 V_(L)35 CDRL1-75 RSSQSLLNSDDGNTYLD 67C10V_(L)36 63F9 889 V_(L)38 CDRL1-76 RASQDIRNDLA 67F6v1 890 V_(L)39CDRL1-77 RSSQSLLNSDAGTTYLD 50G5v2 891 V_(L)94 CDRL1-78 RSSQRLVYSDGNTYLN48G4 892 V_(L)89 CDRL1-79 RASQSVASSYLV 53C3.1 V_(L)89 58C2 893 V_(L)91CDRL1-81 RSSQSLFDNDDGDTYLD 68G8v2 1872 V_(L)105 CDRL1-82 RASQGIRSGLG68G8v3 V_(L)106 65B7v1 1873 V_(L)29 CDRL1-83 RASQSVSSIYLA 67F6v2 1874V_(L)108 CDRL1-84 RSSQSLLNSDAGTTYLD 65B7v2 1875 V_(L)107 CDRL1-85RSSQSLVYSDGDTYLN 65H11v2 1876 V_(L)103 CDRL1-86 SGDKLGDRYVC 63A10v3 1877V_(L)102 CDRL1-87 SGDKLGNRYTC 48C9 894 V_(L)78 CDRL2-1 VASSLES 49A12V_(L)78 51E2 V_(L)78 48F3 895 V_(L)77 CDRL2-2 AVSSLQS 48F8 896 V_(L)49CDRL2-3 FASQSFS 53B9 V_(L)49 56B4 V_(L)49 57E7 V_(L)49 57F11 V_(L)4948H11 897 V_(L)40 CDRL2-4 GASNLQS 49A10 898 V_(L)65 CDRL2-5 TLSYRAS 48D4V_(L)65 49G2 V_(L)66 50C12 V_(L)66 55G11 V_(L)66 60D7 V_(L)69 67A5V_(L)35 67C10 V_(L)36 50G1 V_(L)90 58C2 V_(L)91 49C8 899 V_(L)45 CDRL2-6DVSNLET 52H1 V_(L)45 54A1 V_(L)44 55G9 V_(L)44 49G3 900 V_(L)47 CDRL2-7DASNLET 56E7 V_(L)86 49H12 901 V_(L)43 CDRL2-8 DTFILET 51A8 902 V_(L)61CDRL2-9 EDKERSS 51C10.1 903 V_(L)55 CDRL2-10 EDSKRPS 59D10v1 V_(L)5651C10.2 904 V_(L)70 CDRL2-11 QDTKRPS 59G10.2 V_(L)60 51E5 905 V_(L)79CDRL2-12 AASSLQF 51G2 906 V_(L)51 CDRL2-13 DASSLQS 52A8 907 V_(L)41CDRL2-14 AASSLQS 52C5 V_(L)73 53H5.2 V_(L)62 55D3 V_(L)71 56G1 V_(L)7657B12 V_(L)72 63E6 V_(L)6 66F7 V_(L)7 66D4 V_(L)18 50G5 v1 V_(L)93 51C1V_(L)95 55A7 V_(L)98 61E1 V_(L)100 60G5.1 V_(L)74 52B8 908 V_(L)82CDRL2-15 GASTRAT 53H5.3 V_(L)80 65F9 V_(L)31 52C1 909 V_(L)67 CDRL2-16DNNKRPS 59G10.3 V_(L)54 68C8 V_(L)34 52F8 910 V_(L)42 CDRL2-17 LGSNRAS55E9 V_(L)68 52H2 911 V_(L)84 CDRL2-18 GASRRAT 53F6 912 V_(L)63 CDRL2-19LDSNRAS 54H10.1 913 V_(L)53 CDRL2-20 GASSRAT 55D1 V_(L)53 48H3 V_(L)5353C11 V_(L)53 57D9 V_(L)87 61H5 V_(L)88 52B9 V_(L)88 63F5 V_(L)14 64A7V_(L)17 65B7 V_(L)29 55E6 V_(L)99 55E4 914 V_(L)75 CDRL2-21 TASSLQS49B11 V_(L)75 50H10 V_(L)75 53C1 V_(L)75 50G5v2 915 V_(L)94 CDRL2-22KVSNWDS 65B7v2 55G5 916 V_(L)83 CDRL2-23 QDNKRPS 56A7 917 V_(L)52CDRL2-24 DASTLQS 56E4 V_(L)52 56C11 918 V_(L)64 CDRL2-25 DDSDRPS 67A4V_(L)20 65B4 V_(L)21 56G3.2 919 V_(L)85 CDRL2-26 GASSRDT 56G3.3 920V_(L)81 CDRL2-27 GASARAT 55B10 V_(L)81 59A10 921 V_(L)48 CDRL2-28GASSLQS 49H4 V_(L)48 59C9 922 V_(L)50 CDRL2-29 AASNLQR 58A5 V_(L)50 57A4V_(L)50 57F9 V_(L)50 63G8v1 V_(L)1 63G8v2 V_(L)1 63G8v3 V_(L)1 64A8V_(L)2 67B4 68D3 59D10 v2 923 V_(L)57 CDRL2-30 QNNKRPS 60F9 924 V_(L)58CDRL2-31 GSSNRAT 48B4 V_(L)58 52D6 V_(L)58 60G5.2 925 V_(L)46 CDRL2-32QDSKRPS 65D1 V_(L)27 65H11v2 61G5 926 V_(L)59 CDRL2-33 GASNRAT 64E6 927V_(L)3 CDRL2-34 GAFSRAS 65E8 V_(L)3 65F11 V_(L)3 67G7 V_(L)3 63H11V_(L)3 63B6 928 V_(L)4 CDRL2-35 GAFSRAT 64D4 V_(L)4 65C1 V_(L)16 66F6V_(L)15 48G4 V_(L)89 53C3.1 V_(L)89 65C3 929 V_(L)5 CDRL2-36 GASNRAI68D5 V_(L)5 64H5 930 V_(L)8 CDRL2-37 RDSKRPS 65G4 V_(L)8 67G8 V_(L)2864H6 V_(L)37 67G10 v1 931 V_(L)9 CDRL2-38 SDSNRPS 65H11 V_(L)23 67G10 v2932 V_(L)10 CDRL2-39 QDNERPS 66B4 933 V_(L)11 CDRL2-40 AASSLKS 66G2 934V_(L)12 CDRL2-41 AASNLQS 68G5 935 V_(L)13 CDRL2-42 RDRNRPS 65E3 V_(L)2565D4 V_(L)26 65B1 936 V_(L)19 CDRL2-43 TTSSLQS 53C3.2 937 V_(L)96CDRL2-44 GTSIRAS 63A10v1 938 V_(L)22 CDRL2-45 CDSNRPS 63A10v2 V_(L)10154H10.3 939 V_(L)97 CDRL2-46 SASSLQS 64C8 940 V_(L)24 CDRL2-47 KGSNWDS64A6 941 V_(L)30 CDRL2-48 GTSTRAT 67F5 942 V_(L)32 CDRL2-49 GSSNRAI64B10 943 V_(L)33 CDRL2-50 DNDKRPS 63F9 944 V_(L)38 CDRL2-51 ASSSLQS67F6 945 V_(L)39 CDRL2-52 TLSFRAS 67F6v2 50D4 946 V_(L)92 CDRL2-53AASTLLS 63A10v3 1878 V_(L)102 CDRL2-54 QDSERPS 48C9 947 V_(L)78 CDRL3-1QQSDSIPRT 49A12 51E2 48F3 948 V_(L)77 CDRL3-2 QQSYSATFT 48F8 949 V_(L)49CDRL3-3 HQSSDLPLT 53B9 V_(L)49 56B4 V_(L)49 57E7 V_(L)49 57F11 V_(L)4948H11 950 V_(L)40 CDRL3-4 QQSYNTPCS 49A10 951 V_(L)65 CDRL3-5 MQRIEFPIT48D4 V_(L)65 67C10 V_(L)36 67F6v1 V_(L)39 67F6v1 V_(L)39 49C8 952V_(L)45 CDRL3-6 QQYDNLPFT 52H1 V_(L)45 49G2 953 V_(L)66 CDRL3-7MQHIEFPST 50C12 V_(L)66 55G11 V_(L)66 49G3 954 V_(L)47 CDRL3-8 HQYDDLPLT49H12 955 V_(L)43 CDRL3-9 QQYDNLPLT 54A1 V_(L)44 55G9 V_(L)44 51A8 956V_(L)61 CDRL3-10 QSYDRNNHVV 51C10.1 957 V_(L)55 CDRL3-11 YSTDSSVNHVV51C10.2 958 V_(L)70 CDRL3-12 QAWDSGTVV 51E5 959 V_(L)79 CDRL3-13LQHSSYPLT 51G2 960 V_(L)51 CDRL3-14 QQTNSFPPWT 56A7 V_(L)52 56E4 V_(L)5259A10 V_(L)48 49H4 V_(L)48 59C9 V_(L)50 58A5 V_(L)50 57A4 V_(L)50 57F9V_(L)50 52A8 961 V_(L)41 CDRL3-15 QQSYSTPLT 65B1 V_(L)19 52B8 962V_(L)82 CDRL3-16 QQYNNWPLT 56G3.2 V_(L)85 52C1 963 V_(L)67 CDRL3-17GTWDSSLSAVV 64B10 V_(L)33 68C8 V_(L)34 52C5 964 V_(L)73 CDRL3-18QQSSSIPWT 55E4 V_(L)75 49B11 V_(L)75 50H10 V_(L)75 53C1 V_(L)75 51C1V_(L)95 60G5.1 V_(L)74 52F8 965 V_(L)42 CDRL3-19 MQALQTPFT 52H2 966V_(L)84 CDRL3-20 QQYGSSPRS 53F6 967 V_(L)63 CDRL3-21 MQGLQTPPT 53H5.2968 V_(L)62 CDRL3-22 LQHKSYPFT 53H5.3 969 V_(L)80 CDRL3-23 QQFSNSIT54H10.1 970 V_(L)53 CDRL3-24 QQYGSSRT 55D1 V_(L)53 48H3 V_(L)53 53C11V_(L)53 55D3 971 V_(L)71 CDRL3-25 QQYNIYPRT 55E9 972 V_(L)68 CDRL3-26MQALQTLIT 55G5 973 V_(L)83 CDRL3-27 QAWDSATVI 56C11 974 V_(L)64 CDRL3-28QVWDSSSDVV 56E7 975 V_(L)86 CDRL3-29 QQYAILPFT 56G1 976 V_(L)76 CDRL3-30QQSSTIPWT 56G3.3 977 V_(L)81 CDRL3-31 QQYGRSLFT 55B10 V_(L)81 61H5V_(L)88 52B9 V_(L)88 57B12 978 V_(L)72 CDRL3-32 QQYNTYPRT 57D9 979V_(L)87 CDRL3-33 HQYGTSPCS 59D10 v1 980 V_(L)56 CDRL3-34 YSTDSSGNHVV59D10 v2 981 V_(L)57 CDRL3-35 QAWDSSTAV 59G10.2 982 V_(L)60 CDRL3-36QAWDSSTTWV 59G10.3 983 V_(L)54 CDRL3-37 GTWDSSLSVMV 60D7 984 V_(L)69CDRL3-38 MQRIEFPLT 50G1 V_(L)90 60F9 985 V_(L)58 CDRL3-39 QQYGSSPPWT48B4 V_(L)58 52D6 V_(L)58 61G5 V_(L)59 60G5.2 986 V_(L)46 CDRL3-40QAWDSSTWV 63G8v1 987 V_(L)1 CDRL3-41 LQHNSYPLT 63G8v2 V_(L)1 64A8 V_(L)167B4 V_(L)1 68D3 V_(L)2 64E6 988 V_(L)3 CDRL3-42 QQFGSSLT 65E8 V_(L)365F11 V_(L)3 67G7 V_(L)3 63H11 V_(L3) 63F5 V_(L)14 65C1 V_(L)16 66F6V_(L)15 63B6 989 V_(L)4 CDRL3-43 QQFGRSFT 64D4 V_(L)4 65C3 990 V_(L)5CDRL3-44 QQYNNWPWT 68D5 V_(L)5 63E6 991 V_(L)6 CDRL3-45 QQSYSTSLT 66F7V_(L)7 64H5 992 V_(L)8 CDRL3-46 QVWDSSSVV 65G4 V_(L)8 67G10 v1 993V_(L)9 CDRL3-47 QVWDSSSDGV 67G10 v2 994 V_(L)10 CDRL3-48 QAWDSTTVV64A10v3 64A7 995 V_(L)17 CDRL3-49 QQYGSSSLCS 66B4 996 V_(L)11 CDRL3-50QQANSFPPT 66G2 997 V_(L)12 CDRL3-51 LQLNGYPLT 68G5 998 V_(L)13 CDRL3-52QLWDSSTVV 66D4 999 V_(L)18 CDRL3-53 QQSYSSPLT 54H10.3 V_(L)97 55A7 1000V_(L)98 CDRL3-54 QQTYSAPFT 67A4 1001 V_(L)20 CDRL3-55 QVWDSSSDHVV 65B4V_(L)21 63A10 1002 V_(L)22 CDRL3-56 HACGSSSSDGV 65H11 1003 V_(L)23CDRL3-57 QVWDSSCDGV 64C8 1004 V_(L)24 CDRL3-58 IQDTHWPTCS 65E3 1005V_(L)25 CDRL3-59 QVWDSSTVV 67G8 V_(L)28 65D4 1006 V_(L)26 CDRL3-60QVWDSNPVV 65D1 1007 V_(L)27 CDRL3-61 QAWDSRV 65B7v1 1008 V_(L)29CDRL3-62 QQYGSSCS 64A6 1009 V_(L)30 CDRL3-63 QQYNTWPWT 65F9 V_(L)31 67F51010 V_(L)32 CDRL3-64 QQYEIWPWT 55E6 1011 V_(L)99 CDRL3-65 QQYGSSPWT67A5 1012 V_(L)35 CDRL3-66 MQRLEFPIT 58C2 V_(L)91 61E1 1013 V_(L)100CDRL3-67 QQSFSTPLT 64H6 1014 V_(L)37 CDRL3-68 QVWDSSPVV 63F9 1015V_(L)38 CDRL3-69 LQRNSYPLT 53C3.2 1016 V_(L)96 CDRL3-70 HQYTNWPRT 48G41017 V_(L)89 CDRL3-71 QQYGTSPFT 53C3.1 V_(L)89 50G5 v1 1018 V_(L)93CDRL3-72 LQHNSYPRT 50D4 1019 V_(L)92 CDRL3-74 QKYYSAPFT 50G5 v2 1020V_(L)94 CDRL3-75 MEGTHWPRD 63G8v3 1879 V_(L)106 CDRL3-76 LQHNTYPLT65B7v2 1880 V_(L)107 CDRL3-77 MQGTHWRGWT 65H11v2 1881 V_(L)103 CDRL3-78QAWDSITVV 63A10v1 1882 V_(L)22 CDRL3-79 QVWDSSSDGV

TABLE 3C Coding Sequences for CDRHs SEQ Contained ID in Clone NO:Reference Designation Coding Sequences 48C9 1021 V_(H)73 CDRH1-1GGTTACTACTGGACC 49A12 V_(H)73 51E2 V_(H)73 48F3 1022 V_(H)72 CDRH1-2GGTTACTACTGGAGC 51E5 V_(H)74 52C5 V_(H)70 55E4 V_(H)70 60G50.1 V_(H)7049B11 V_(H)70 50H10 V_(H)70 53C1 V_(H)70 56G1 V_(H)71 51C1 V_(H)89 48F81023 V_(H)48 CDRH1-3 AGCTATAGCATGAAC 51G2 V_(H)50 56A7 V_(H)51 53B9V_(H)48 56B4 V_(H)48 57E7 V_(H)48 57F11 V_(H)48 56E4 V_(H)51 55E6V_(H)93 48H11 1024 V_(H)39 CDRH1-4 GGCTACTATAAGCAC 48G4 1025 V_(H)83CDRH1-5 GAATTATCCATACAC 49A10 1026 V_(H)62 CDRH1-6 AACTATGGCATGCAC 58C2V_(H)85 59G10.2 V_(H)57 48D4 V_(H)62 49C8 1027 V_(H)44 CDRH1-7AGTTATGATATCGAC 52H1 49G2 1028 V_(H)63 CDRH1-8 AACTATGGCATGCGC 50C12V_(H)63 55G11 V_(H)63 49G3 1029 V_(H)46 CDRH1-9 AATCCTAGAATGGGTGTGAGC49H12 1030 V_(H)42 CDRH1-10 AGTTACGATATCAAC 54A1 V_(H)43 55G9 V_(H)4350G1 1031 V_(H)84 CDRH1-11 AGCTATGGCCTGCAC 51A8 1032 V_(H)58 CDRH1-12AGCTATGGCATGCAC 52C1 V_(H)64 53H5.2 V_(H)59 56C11 V_(H)61 60D7 V_(H)6664H5 V_(H)7 65G4 V_(H)8 66G2 V_(H)11 68G5 V_(H)12 64C8 V_(H)23 67G8V_(H)27 68D3v2 V_(H)8 51C10.1 1033 V_(H)54 CDRH1-13 AACTATGCCATGAGC59D10v1 V_(H)54 59D10v2 V_(H)54 51C10.2 1034 V_(H)67 CDRH1-14AGTGGTGGTTACTACTGGAGC 64A6 V_(H)29 52A8 1035 V_(H)40 CDRH1-15GGCTACTATTTGCAC 66B4 V_(H)10 52B8 1036 V_(H)77 CDRH1-16 TATTATTACTGGAGT52F8 1037 V_(H)41 CDRH1-17 GGCTACTATACACAC 52H2 1038 V_(H)79 CDRH1-18ACTTACTACTGGAGC 53F6 1039 V_(H)60 CDRH1-19 ACCTATGGCATGCAC 53H5.3 1040V_(H)75 CDRH1-20 GATTACTACTGGAAC 54H10.1 1041 V_(H)52 CDRH1-21AGCTATGCCATGAGC 60F9 V_(H)55 61G5 V_(H)56 55D1 V_(H)52 48H3 V_(H)5253C11 V_(H)52 48B4 V_(H)55 52D6 V_(H)55 55D3 1042 V_(H)68 CDRH1-22AGTGGTGTTTACTACTGGAAC 55E9 1043 V_(H)65 CDRH1-23 AGCTTTGGCATGCAC 55G51044 V_(H)78 CDRH1-24 AGTTACTACTGGAGC 65C3 V_(H)5 68D5 V_(H)5 67F5V_(H)31 55A7 V_(H)92 56E7 1045 V_(H)81 CDRH1-25 AGCTACTGGATCGGC 67A5V_(H)34 67C10 V_(H)35 64H6 V_(H)36 56G3.2 1046 V_(H)80 CDRH1-26AGTTACTACTGGAAC 56G3.3 1047 V_(H)76 CDRH1-27 AGTAGTAGTTACTACTGGGGC 55B10V_(H)76 61H5 V_(H)86 52B9 V_(H)86 57B12 1048 V_(H)69 CDRH1-28AGTGGTGTTTACTACTGGAGC 57D9 1049 V_(H)82 CDRH1-29 AGCAACAGTGCTACTTGGAAC59A10 1050 V_(H)47 CDRH1-30 GACTCCTACATGAGC 49H4 59C9 1051 V_(H)49CDRH1-31 AGCTATAGCATGAGT 58A5 V_(H)49 57A4 V_(H)49 57F9 V_(H)49 59G10.31052 V_(H)53 CDRH1-32 CACTATGCCATGAGC 60G5.2 1053 V_(H)45 CDRH1-33AACTATGGTATCAGC 63G8 1054 V_(H)1 CDRH1-34 AGCTATGGCATACAC 64A8 V_(H)167B4 V_(H)1 68D3 V_(H)1 64E6 1055 V_(H)2 CDRH1-35 AGTGGTGATTACTACTGGACC65E8 V_(H)2 65F11 V_(H)2 67G7 V_(H)2 63H11 V_(H)3 63F5 V_(H)13 65C1V_(H)15 66F6 V_(H)14 63B6 1056 V_(H)4 CDRH1-36 AGTGGTGATTACTACTGGAGC64D4 V_(H)4 65F9 V_(H)30 64B10v1 V_(H)32 64B10v1 V_(H)32 63E6 1057V_(H)6 CDRH1-37 AGTGGTGATTACTACTGGACC 66F7 V_(H)6 50G5 v1 V_(H)88 50G5v2 V_(H)88 67G10v1 1058 V_(H)9 CDRH1-38 AACGCCTGGATGAGT 67G10v2 V_(H)963A10 V_(H)21 65H11 V_(H)22 53C3.2 1059 V_(H)90 CDRH1-39AGTGGTAATTACTACTGGAGC 64A7 1060 V_(H)16 CDRH1-40 AGTGATACTTCCTACTGGGGC50D4 1061 V_(H)87 CDRH1-41 AGTCATGATATCAAC 61E1 1062 V_(H)94 CDRH1-42AGCAACAGTGCTGCTTGGAAC 66D4 1063 V_(H)17 CDRH1-43 GGCTACTATATACAC 54H10.3V_(H)91 65B1 1064 V_(H)18 CDRH1-44 GGCTACTTTATGCAC 67A4 1065 V_(H)19CDRH1-45 ACCTACGACATGCAC 65B4 1066 V_(H)20 CDRH1-46 AGTTACGACATGCAC 65E31067 V_(H)24 CDRH1-47 AACTATAACATGCAC 65D4 1068 V_(H)25 CDRH1-48TTCTATGGCATGCAC 65D1 1069 V_(H)26 CDRH1-49 TACTATTACATTCAC 65B7 1070V_(H)28 CDRH1-50 AGTGATGCTTACTACTGGAGC 68C8 1071 V_(H)33 CDRH1-51AGTGGTGATAACTACTGGAGC 63F9 1072 V_(H)37 CDRH1-52 AGTGGTGGTTACTACTGGAAC67F6 1073 V_(H)38 CDRH1-53 GGCTACTGGATCGGC 48C9 1074 V_(H)73 CDRH2-1GAAATCAATCATAGTGAAAACACCAACT 52C5 V_(H)70 ACAACCCGTCCCTCAAGAGT 55E4V_(H)70 56G1 V_(H)71 49A12 V_(H)73 51E2 V_(H)73 60G5.1 V_(H)70 49B11V_(H)70 50H10 V_(H)70 53C1 V_(H)70 51C1 V_(H)89 48F3 1075 V_(H)72CDRH2-2 GAAATCACTCATACTGGAAGCTCCAACT ACAACCCGTCCCTCAAGAGT 48F8 1076V_(H)48 CDRH2-3 TCCATTAGTAGTAGTAGTAGTTACGAATA 53B9 V_(H)48CTACGTAGACTCAGTGAAGGGC 56B4 V_(H)48 57E7 V_(H)48 57F11 V_(H)48 48H111077 V_(H)39 CDRH2-4 TGGATCAACCCTAACAGTGGTGCCACAAAGTATGCACAGAAGTTTCAGGGC 48G4 1078 V_(H)83 CDRH2-5GGTTTTGATCCTGAAGATGGTGAAACAA 53C3.1 TCTACGCACAGAAGTTCCAGGGC 49A10 1079V_(H)62 CDRH2-6 ATTATATGGTATGATGGAAGTAATAAAA 48D4 V_(H)62ACTATGCAGACTCCGTGAAGGGC 49C8 1080 V_(H)44 CDRH2-7TGGATGAACCCTAACGGTGGTAACACAG GCTATGCACAGAAGTTCCAGGGC 49G2 1081 V_(H)63CDRH2-8 CTTATATGGTATGATGGAAGTAATAAGTT 50C12 V_(H)63CTATGCAGACTCCGTGAAGGGC 55G11 V_(H)63 49G3 1082 V_(H)46 CDRH2-9CACATTTTTTCGAATGACGAAAAATCCTA CAGCACATCTCTGAAGAGC 49H12 1083 V_(H)42CDRH2-10 TGGATGAACCCCTACAGTGGGAGCACAG GCTATGCACAGAATTTCCAGGGC 50G1 1084V_(H)84 CDRH2-11 GTTATATGGAATGATGGAAGTAATAAGC TTTATGCAGACTCCGTGAAGGGC51A8 1085 V_(H)58 CDRH2-12 GTTATATCATATGATGGAAGTAATAAAT 63G8 V_(H)1ACTATGCAGACTCCGTGAAGGGC 64A8 V_(H)1 67B4 V_(H)1 68D3 V_(H)1 51C10.1 1086V_(H)54 CDRH2-13 GGTATTAGTGGTAGTAGTGCTGGCACAT 59D10v1 V_(H)54ACTACGCAGACTCCGTGAAGGGC 59D10v2 V_(H)54 51C10.2 1087 V_(H)67 CDRH2-14TACATCTATTACAATGGGAGTCCCTACGA CAACCCGTCCCTCAAGAGG 51E5 1088 V_(H)74CDRH2-15 GAACTCGATCATAGTGGAAGTATCAACT ACAACCCGTCCCTCAAGAGT 51G2 1089V_(H)50 CDRH2-16 TCCATTAGTAGTAGTAGTACTTACATATA 56A7 V_(H)51CTACGCAGACTCAGTGAAGGGC 56E4 V_(H)51 52A8 1090 V_(H)40 CDRH2-17TGGATCAACCCTAACAGTGCTGCCACAA ACTATGCACCGAAGTTTCAGGGC 52B8 1091 V_(H)77CDRH2-18 TATATCTATTATAGTGGGAGCACCAACTA 55A7 V_(H)92 CAACCCCTCCCTCAAGAGT52C1 1092 V_(H)64 CDRH2-19 GTTATATGGTATGATGGAAGTAATAACTATTATGCAGACTCCGTGAAGGGC 52F8 1093 V_(H)41 CDRH2-20TGGATCAACCCTAGCAGTGGTGACACAA AGTATGCACAGAAGTTTCAGGGC 52H2 1094 V_(H)79CDRH2-21 TATATCTTTTACAATGGGAACGCCAACTA CAGCCCCTCCCTGAAGAGT 53F6 1095V_(H)60 CDRH2-22 GTTATATGGTATGATGGAAGTAATAAAT 60D7 V_(H)66ACTATGCAGACTCCGTGAAGGGC 65D4 V_(H)25 53H5.2 1096 V_(H)59 CDRH2-23CTTATATCATATGATGGAAGTAATAAATA CTATGCAGACTCCGTGAAGGGC 53H5.3 1097 V_(H)75CDRH2-24 GAAATCAATCATAGTGGAACCACCAACT ACAATCCGTCCCTCAAGAGT 54A1 1098V_(H)43 CDRH2-25 TGGATGAACCCTCACAGTGGTAACACAG 55G9 V_(H)43GCTATGCACAGAAGTTCCAGGGC 54H10.1 1099 V_(H)52 CDRH2-26GCTATTAGTGGTAGTGGTCGTACCACATA 55D1 V_(H)52 CTCCGCAGACTCCGTGAAGGGC 48H3V_(H)52 53C11 V_(H)52 55D3 1100 V_(H)68 CDRH2-27TACCTCTATTACAGTGGGAGCACCTACTA CAACCCGTCCCTCAAGAGT 55E9 1101 V_(H)65CDRH2-28 CTTATATGGTATGATGGAGATAATAAAT ACTATGCAGACTCCGTGAAGGGC 55G5 1102V_(H)78 CDRH2-29 CGTATCTATATCAGTGGGAGCACCAACT ACAACCCCTCCCTCGAGAAT 56C111103 V_(H)61 CDRH2-30 GTTATATGGTATGATGGAAGTTATCAATTCTATGCAGACTCCGTGAAGGGC 56E7 1104 V_(H)81 CDRH2-31ATCATCTATCCTGGTGACTCTGATACCAG 67A5 V_(H)34 ATACAGCCCGTCCTTCCAAGGC 67C10V_(H)35 67F6 V_(H)38 56G3.2 1105 V_(H)80 CDRH2-32CGTATCTATACCAGTGGGAGCACCAACT ACAATCCCTCCCTCAAGAGT 56G3.3 1106 V_(H)76CDRH2-33 ATGATCTATTATAGTGGGACCACCTACTA CAACCCGTCCCTCAAGAGT 57B12 1107V_(H)69 CDRH2-34 TACATCTATTACAGTGGGAGCACCTACTA 63H11 V_(H)3CAACCCGTCCCTCAAGAGT 66F6 V_(H)14 65F9 V_(H)30 57D9 1108 V_(H)82 CDRH2-35AGGACATACTACAGGTCCAAGTGGTATA 61E1 V_(H)94 ATGATTATGCAGTATCTGTGAAAAGT58C2 1109 V_(H)85 CDRH2-36 GTTATATGGAATGATGGAAATAACAAATACTATGCAGACTCCGTGAAGGGC 59A10 1110 V_(H)47 CDRH2-37TCCATTAGTAGTAGTGGTAGTATCGTATA 49H4 CTTCGCAGACTCTGTGAAGGGC 59C9 1111V_(H)49 CDRH2-38 TCCATTAGTAGTAGTAGTACTTACATATA 58A5 V_(H)49CTACGCAGACTCACTGAAGGGC 57A4 V_(H)49 57F9 V_(H)49 59G10.2 1112 V_(H)57CDRH2-39 ATTACATCATATGGAGGAAGTAATAAAA ATTATGCAGACTCCGTGAAGGGC 59G10.31113 V_(H)53 CDRH2-40 GCTATTAGTGGTAGTGGTGCTGGCACATTCTACGCGGACTCCATGAAGGGC 60F9 1114 V_(H)55 CDRH2-41GTTATTAGTGACAGTGGTGGTAGCACAT 48B4 V_(H)55 ACTACGCAGACTCCGTGAAGGGC 52D6V_(H)55 60G5.2 1115 V_(H)45 CDRH2-42 TGGATCAGCGCTTACAATGGTTACTCAAACTATGCACAGAAGTTCCAGGAC 61G5 1116 V_(H)56 CDRH2-43GTTATTAGTGGTAGTGGTGGTGACACATA CTACGCAGACTCCGTGAAGGGC 64E6 1117 V_(H)2CDRH2-44 TACATCTATTACACTGGGAGCACCTACTA 65E8 V_(H)2 CAACCCGTCCCTCAAGAGT65F11 V_(H)2 67G7 V_(H)2 63B6 1118 V_(H)4 CDRH2-45TACATCTATTACAGTGGGACCACCTACTA 64D4 V_(H)4 CAACCCGTCCCTCAAGAGT 65C3 1119V_(H)5 CDRH2-46 TATATCTATTACACTGGGAGCACCAACTA 68D5 V_(H)5CAACCCCTCCCTCAAGAGT 63E6 1120 V_(H)6 CDRH2-47TGGATGAACCCTAATAGTGGTGCCACAA 66F7 V_(H)6 AGTATGCACAGAAGTTTCAGGGC 64H51121 V_(H)7 CDRH2-48 GTTATATGGGATGATGGAAGTAATAAAT 65G4 V_(H)8ACTATGCAGACTCCGTGAAGGGC 67G10v1 1122 V_(H)9 CDRH2-49CGTATTAAAAGCAAAACTGATGGTGGGA 67G10v2 V_(H)9CAACAGAGTACGCTGCACCCGTGAAAGGC 63F5 1123 V_(H)13 CDRH2-50TACATCTATTACAGTGGGAGCGCCTACTA CAACCCGTCCCTCAAGAGT 64A7 1124 V_(H)16CDRH2-51 AATATCTATTATAGTGGGACCACCTACTT CAACCCGTCCCTCAAGAGT 65C1 1125V_(H)15 CDRH2-52 TACATTTTTTACAGTGGGAGCACCTACTA 65B7 V_(H)28CAACCCGTCCCTCAAGAGT 66B4 1126 V_(H)10 CDRH2-53TGGATCAACCCTAACAGTGGTGGCACAG ACTATGCACAGAAGTTTCAGGGC 66G2 1127 V_(H)11CDRH2-54 GGTATATCATATGATGGAAGTAATAAAA ACTATGCAGACTCCGTGAAGGGC 68G5 1128V_(H)12 CDRH2-55 GTTATATGGTATGATGGAAGTAATAAAT ACCATGCAGACTCCGTGAAGGGC66D4 1129 V_(H)17 CDRH2-56 TGGATCAACCCTCCCAGTGGTGCCACAAACTATGCACAGAAGTTTCGGGGC 65B1 1130 V_(H)18 CDRH2-57TGGATCAACCCTAACAGTGGTGCCACAA ACTATGCACAGAAGTTTCACGGC 67A4 1131 V_(H)19CDRH2-58 GCTATTGGTATTGCTGGTGACACATACTA TTCAGACTCCGTGAAGGGC 65B4 1132V_(H)20 CDRH2-59 ACTATTGATACTGCTGGTGACGCTTACTA TCCAGGCTCCGTGAAGGGC 63A101133 V_(H)21 CDRH2-60 CGTATTAAAAGCAAAACTGATGGTGGGA 67G10v1 V_(H)9CAACAGACTACGCTGCACCCGTGAAAGGC 67G10v2 V_(H)9 65H11 1134 V_(H)22 CDRH2-61CGTATTATAGGCAAAACTGATGGTGGGA CAACAGACTACGCTGCACCCGTGAAAGGC 64C8 1135V_(H)23 CDRH2-62 GTTATATCATATGATGGAAGTAACAAAC ACTATGCAGACTCCGTGAAGGGC65E3 1136 V_(H)24 CDRH2-63 GTTTTATGGTATGATGGAAATACTAAATACTATGCAGACTCCGTGAAGGGC 65D1 1137 V_(H)26 CDRH2-64CTTATATGGTATGATGGAAGTAATAAAG ACTATGCAGACTCCGTGAAGGGC 67G8 1138 V_(H)27CDRH2-65 GTTATATGGTATGATGGAAGTAATAAAG ACTATGCAGACTCCGTGAAGGGC 64A6 1139V_(H)29 CDRH2-66 TACATCTATTACAGTGGGGGCACCCACTA CAACCCGTCCCTCAAGAGT 67F51140 V_(H)31 CDRH2-67 TATATCTATTACAGTGGGAACACCAACTA CAACCCCTCCCTCAAGAGT64B10 1141 V_(H)32 CDRH2-68 TTTATCTATTACAGTGGGGGCACCAACTACAACCCCTCCCTCAAGAGT 68C8 1142 V_(H)33 CDRH2-69TTCATGTTTTACAGTGGGAGTACCAACTA CAACCCCTCCCTCAAGAGT 64H6 1143 V_(H)36CDRH2-70 ATCATCTATCCTGGTGACTCTGAAACCAG ATACAGCCCGTCCTTTCAAGGC 63F9 1144V_(H)37 CDRH2-71 TACATCTATGACAGTGGGAGCACCTACT ACAACCCGTCCCTCAAGAGT 61H51145 V_(H)86 CDRH2-72 AGTATCTATTATAGTGGGACCACCTACTA 52B9 V_(H)86CAACCCGTCCCTCAAGAGT 50G5 v1 1146 V_(H)88 CDRH2-73TGGATCAACCCTGACAGTGGTGGCACAA 50G5 v2 V_(H)88 ACTATGCACAGAAGTTTCAGGGC54H10.3 1147 V_(H)91 CDRH2-74 TGGATCAACCCTAACAGTGGTGGCACAAACTATGCACAGAAGTTTCGGGGC 50D4 1148 V_(H)87 CDRH2-75TGGATGAACCCTTACAGTGGTAGCACAG GCCTCGCACAGAGGTTCCAGGAC 55E6 1149 V_(H)93CDRH2-76 TACATTAGTAGTGGTAGTAGTACCATATA CCACGCAGACTCTGTGAAGGGC 53C3.21150 V_(H)90 CDRH2-77 TACATCTATCACAGTGGGAGCGCCTACTA CAACCCGTCCCTCAAGAGT64B10v2 1883 V_(H)96 CDRH2-78 TTTATTTATTACAGTGGGGGCACCAACTACAACCCCCCCCTCAAGAGT 68D3v2 1884 V_(H)95 CDRH2-79TTTATATCATATGCTGGAAGTAATAAATA CTATGCAGACTCCGTGAAGGGC 48C9 1151 V_(H)73CDRH3-1 GAGAGTGGGAACTTCCCCTTTGACTAC 49A12 V_(H)73 51E2 V_(H)73 48F3 1152V_(H)72 CDRH3-2 GGCGGGATTTTATGGTTCGGGGAGCAGG CTTTTGATATC 48F8 1153V_(H)48 CDRH3-3 TCCCTAAGTATAGCAGTGGCTGCCTCTGA 53B9 V_(H)48 CTAC 56B4V_(H)48 57E7 V_(H)48 57F11 V_(H)48 48H11 1154 V_(H)39 CDRH3-4GAGGTACCCGACGGTATAGTAGTGGCTG GTTCAAATGCTTTTGATTTC 48G4 1155 V_(H)83CDRH3-5 CATTCTGGTTCGGGGAGGTTTTACTACTA 53C3.1 CTACTACGGTATGGACGTC 49A101156 V_(H)62 CDRH3-6 GATCAGGATTACGATTTTTGGAGTGGTTA 48D4 V_(H)62TCCTTACTTCTACTACTACGGTATGGACG TC 49C8 1157 V_(H)44 CDRH3-7GGGAAGGAATTTAGCAGGGCGGAGTTTG ACTAC 49G2 1158 V_(H)63 CDRH3-8GATCGGTATTACGATTTTTGGAGTGGTTA 50C12 V_(H)63TCCATACTTCTTCTACTACGGTCTGGACG 55G11 V_(H)63 TC 49G3 1159 V_(H)46 CDRH3-9GTAGATACCTTGAACTACCACTACTACGG TATGGACGTC 49H12 1160 V_(H)42 CDRH3-10TATAATTGGAACTATGGGGCTTTTGATTTC 54A1 V_(H)43 55G9 V_(H)43 50G1 1161V_(H)84 CDRH3-11 GATCAGTATTACGATTTTTGGAGCGGTTACCCATACTATCACTACTACGGTATGGACG TC 51A8 1162 V_(H)58 CDRH3-12GCGGACGGTGACTACCCATATTACTACTA CTACTACGGTATGGACGTC 51C10.1 1163 V_(H)54CDRH3-13 GATTGGAGTATAGCAGTGGCTGGTACTTT 59D10 V_(H)54 TGACTAC v1 59D10V_(H)54 v2 51C10.2 1164 V_(H)67 CDRH3-14 GGGGCCCTCTACGGTATGGACGTC 51E51165 V_(H)74 CDRH3-15 GTCCTGGGATCTACTCTTGACTAT 51G2 1166 V_(H)50CDRH3-16 GATACTTATATCAGTGGCTGGAACTACG GTATGGACGTC 52A8 1167 V_(H)40CDRH3-17 GAGGGTGGAACTTACAACTGGTTCGACC CC 52B8 1168 V_(H)77 CDRH3-18GGAACTAGGGCTTTTGATATC 52C1 1169 V_(H)64 CDRH3-19GATCGGGCGGGAGCCTCTCCCGGAATGG ACGTC 52C5 1170 V_(H)70 CDRH3-20GTAACTGGAACGGATGCTTTTGATTTC 60G5.1 V_(H)70 49B11 V_(H)70 50H10 V_(H)7053C1 V_(H)70 51C1 V_(H)89 55E4 V_(H)70 56G1 V_(H)71 52F8 1171 V_(H)41CDRH3-21 AGTGGCTGGTACCCGTCCTACTACTACGG TATGGACGTC 52H2 1172 V_(H)79CDRH3-22 GAAACGGACTACGGTGACTACGCACGTC CTTTTGAATAC 53F6 1173 V_(H)60CDRH3-23 GGCCACTATGATAGTAGTGGTCCCAGGG ACTAC 53H5.2 1174 V_(H)59 CDRH3-24GAGGCTAACTGGGGCTACAACTACTACG GTATGGACGTC 53H5.3 1175 V_(H)75 CDRH3-25ATATTACGATATTTTGACTGGTTAGAATA CTACTTTGACTAC 61E1 1176 V_(H)94 CDRH3-26GAGGGCAGCTGGTCCTCCTTCTTTGACTAC 54H10.1 1177 V_(H)52 CDRH3-27GAACAGCAGTGGCTGGTTTATTTTGACTAC 55D1 V_(H)52 48H3 V_(H)52 53C11 V_(H)5255D3 1178 V_(H)68 CDRH3-28 GATGGTATTACTATGGTTCGGGGAGTTAC 57B12 V_(H)69TCACTACTACGGTATGGACGTC 55E6 1179 V_(H)93 CDRH3-29GAAGGGTACTATGATAGTAGTGGTTATT ACTACAACGGTATGGACGTC 55E9 1180 V_(H)65CDRH3-30 AACAGTGGCTGGGATTACTTCTACTACTA CGGTATGGACGTC 55G5 1181 V_(H)78CDRH3-31 AGTGGGAGCTACTCCTTTGACTAC 56A7 1182 V_(H)51 CDRH3-32GATATCTATAGCAGTGGCTGGAGCTACG 56E4 V_(H)51 GTATGGACGTC 56C11 1183 V_(H)61CDRH3-33 GATCACGTTTGGAGGACTTATCGTTATAT CTTTGACTAC 56E7 1184 V_(H)81CDRH3-34 GCACAACTGGGGATCTTTGACTAC 50G5 v1 1185 V_(H)88 CDRH3-35GGCGGATACAGCTATGGTTACGAGGACT 50G5 v2 V_(H)88 ACTACGGTATGGACGTC 56G3.21186 V_(H)80 CDRH3-36 GGCCCTCTTTGGTTTGACTAC 56G3.3 1187 V_(H)76 CDRH3-37GTGGCAGCAGTTTACTGGTATTTCGATCTC 55B10 V_(H)76 61H5 V_(H)86 52B9 V_(H)8655A7 1188 V_(H)92 CDRH3-38 GGGATAACTGGAACTATTGACTTC 57D9 1189 V_(H)82CDRH3-39 ATTGTAGTAGTACCAGCTGTTCTCTTTGA CTAC 58C2 1190 V_(H)85 CDRH3-40GATCAGAATTACGATTTTTGGAATGGTTA TCCCTACTACTTCTACTACGGTATGGACG TC 59A101191 V_(H)47 CDRH3-41 GAGACGTTTAGCAGTGGCTGGTTCGATG 49H4 CTTTTGATATC 59C91192 V_(H)49 CDRH3-42 GATCGATGGAGCAGTGGCTGGAACGAAG 58A5 V_(H)49GTTTTGACTAT 57A4 V_(H)49 57F9 V_(H)49 53C3.2 1193 V_(H)90 CDRH3-43ACTACGGGTGCTTCTGATATC 59G10.2 1194 V_(H)57 CDRH3-44GAGGCCGGGTATAGCTTTGACTAC 59G10.3 1195 V_(H)53 CDRH3-45GATCTTAGAATAGCAGTGGCTGGTTCATT TGACTAC 60D7 1196 V_(H)66 CDRH3-46GATCTTAGAATAGCAGTGGCTGGTTCATT TGACTAC 60F9 1197 V_(H)55 CDRH3-47GATCAGTATTTCGATTTTTGGAGTGGTTA 48B4 V_(H)55 TCCTTTCTTCTACTACTACGGTATGGACG52D6 V_(H)55 TC 60G5.2 1198 V_(H)45 CDRH3-48GATCATAGCAGTGGCTGGTACTACTACG GTATGGACGTC 61G5 1199 V_(H)56 CDRH3-49GATCATACCAGTGGCTGGTACTACTACG GTATGGACGTC 63G8 1200 V_(H)1 CDRH3-50ACGGTGACTAAGGAGGACTACTACTACT 64A8 V_(H)1 ACGGTATGGACGTC 67B4 V_(H)1 68D3V_(H)1 66G2 V_(H)11 64E6 1201 V_(H)2 CDRH3-51ATGACTACCCCTTACTGGTACTTCGATCTC 65E8 V_(H)2 65F11 V_(H)2 67G7 V_(H)263H11 V_(H)3 63F5 V_(H)13 66F6 V_(H)14 63B6 1202 V_(H)4 CDRH3-52ATGACTACTCCTTACTGGTACTTCGGTCTC 64D4 V_(H)4 65C3 1203 V_(H)5 CDRH3-53GAATATTACTATGGTTCGGGGAGTTATTA 68D5 V_(H)5 TCCT 67F5 V_(H)5 63E6 1204V_(H)6 CDRH3-54 GAACTCGGTGACTACCCCTTTTTTGACTAC 66F7 V_(H)6 64H5 1205V_(H)7 CDRH3-55 GAATACGTAGCAGAAGCTGGTTTTGACT 65G4 V_(H)8 AC 67G10v1 1206V_(H)9 CDRH3-56 GATAGTAGTGGGAGCTACTACGTGGAGG 67G10v2 V_(H)9ACTACTTTGACTAC 63A10 V_(H)21 65H11 V_(H)22 64A7 1207 V_(H)16 CDRH3-57CTCCGAGGGGTCTACTGGTACTTCGATCTC 65C1 1208 V_(H)15 CDRH3-58ATGACTTCCCCTTACTGGTACTTCGATCTC 66B4 1209 V_(H)10 CDRH3-59GACGCAGCAACTGGTCGCTACTACTTTGA CAAC 68G5 1210 V_(H)12 CDRH3-60GATCCTGGATACAGCTATGGTCACTTTGA CTAC 66D4 1211 V_(H)17 CDRH3-61GAGACTGGAACTTGGAGCTTCTTTGACTAC 65B1 1212 V_(H)18 CDRH3-62GAACTGGGGATCTTCAACTGGTTCGACCCC 67A4 1213 V_(H)19 CDRH3-63GATCGGAGCAGTGGCCGGTTCGGGGACT ACTACGGTATGGACGTC 65B4 1214 V_(H)20CDRH3-64 GATCGGAGCAGTGGCCGGTTCGGGGACT TCTACGGTATGGACGTC 64C8 1215V_(H)23 CDRH3-65 GAATTACTATGGTTCGGGGAGTATGGGG TAGACCACGGTATGGACGTC 65E31216 V_(H)24 CDRH3-66 GATGTCTACGGTGACTATTTTGCGTAC 65D4 1217 V_(H)25CDRH3-67 GCCCTCAACTGGAACTTTTTTGACTAC 65D1 1218 V_(H)26 CDRH3-68GAAGGGACAACTCGACGGGGATTTGACT AC 67G8 1219 V_(H)27 CDRH3-69TCAGCAGTGGCTTTGTACAACTGGTTCGA CCCC 65B7 1220 V_(H)28 CDRH3-70GAGTCTAGGATATTGTACTTCAACGGGTA CTTCCAGCAC 64A6 1221 V_(H)29 CDRH3-71GTCCTCCATTACTCTGATAGTCGTGGTTA CTCGTACTACTCTGACTTC 65F9 1222 V_(H)30CDRH3-72 GTCCTCCATTACTATGATAGTAGTGGTTA CTCGTACTACTTTGACTAC 64B10 1223V_(H)32 CDRH3-73 TATAGCAGCACCTGGGACTACTATTACG GTGTGGACGTC 68C8 1224V_(H)33 CDRH3-74 TATAGGAGTGACTGGGACTACTACTACG GTATGGACGTC 67A5 1225V_(H)34 CDRH3-75 CGGGCCTCACGTGGATACAGATTTGGTCT TGCTTTTGCGATC 67C10 1226V_(H)35 CDRH3-76 CGGGCCTCACGTGGATACAGATATGGTC TTGCTTTTGCTATC 64H6 1227V_(H)36 CDRH3-77 GTAGCAGTGTCTGCCTTCAACTGGTTCGA CCCC 63F9 1228 V_(H)37CDRH3-78 GATGTTCTAATGGTGTATACTAAAGGGG GCTACTACTATTACGGTGTGGACGTC 67F61229 V_(H)38 CDRH3-79 CGGGCCTCACGTGGATACAGCTATGGTC ATGCTTTTGATTTC 50D41230 V_(H)87 CDRH3-80 GACCTTAGCAGTGGCTACTACTACTACGG TTTGGACGTG 54H10.31231 V_(H)91 CDRH3-81 GAGGAAGACTACAGTGACCACCACTACT TTGACTAC 66D4 1885V_(H)17 CDRH3-82 GAGACTGGAACTTGGAACTTCTTTGACTAC 68D3v2 1886 V_(H)95CDRH3-83 ACGGTGACTGAGGAGGACTACTACTACT ACGGTATGGACGTC

TABLE 3D Coding Sequences for CDRLs SEQ Contained ID in Clone NO:Reference Designation Coding Sequence 48C9 1232 V_(L)78 CDRL1-1CGGGCAAGTCAGAACATTAGGACCT 49A12 ATTTAAAT 51E2 48F3 1233 V_(L)77 CDRL1-2CGGGCAAGTCAGAGGATTAGCAGTT ATTTAAAT 48F8 1234 V_(L)49 CDRL1-3CGGGCCAGTCAGGACATTGGTAATA 53B9 GCTTACAC 56B4 57E7 57F11 48H11 1235V_(L)40 CDRL1-4 CGGGCAAGTCAGAACATTAGGAGCT ATTTAAAT 49A10 1236 V_(L)65CDRL1-5 AGGTCTAGTCAGAGCCTCTTGGATAG 48D4 TGATGATGGAAACACCTATTTGGAC 49C81237 V_(L)45 CDRL1-6 CAGGCGAGTCAGGACATTAACATCTA 52H1 TTTAAAT 49G2 1238V_(L)66 CDRL1-7 AGGTCTAGTCAGAGCCTCTTGGATAG 50C12 V_(L)66TGATGATGGAGACACCTATTTGGAC 55G11 V_(L)66 50G1 V_(L)90 60D7 V_(L)69 49G31239 V_(L)47 CDRL1-8 CAGGCGAGTCAGGGCATTAGCAACT ATTTAAAT 49H12 1240V_(L)43 CDRL1-9 CAGGCGAGTCAAGACATTACCAAAT ATTTAAAT 51A8 1241 V_(L)61CDRL1-10 ACCCGCAGCAGTGGCAGCATTGCCA GCGACTATGTGCAG 51C10.1 1242 V_(L)55CDRL1-11 TCTGGAGATGCATTGCCAAAAAAATA TGCTTAT 51C10.2 1243 V_(L)70CDRL1-12 TCTGGAGATAAATTGGGGGATAAAT ACGTTTGC 51E5 1244 V_(L)79 CDRL1-13CGGGCAAGTCAGGACATTAGAAATG 63G8v1 V_(L)1 ATTTAGGC 64A8 V_(L)1 67B4 V_(L)168D3 V_(L)2 51G2 1245 V_(L)51 CDRL1-14 CGGGCGAGTCAGGGTATTAGCAGCTGGTTAGCC 52A8 1246 V_(L)41 CDRL1-15 CGGGCAAGTCAGACTATTAGCAGTTA TTTAAAT52B8 1247 V_(L)82 CDRL1-16 AGGGCCAGTCAGAGTGTTAGCGACA TCTTAGCC 52C1 1248V_(L)67 CDRL1-17 TCTGGAAGCAGCTCCAACATTGGGAT TAATTATGTATCC 52C5 1249V_(L)73 CDRL1-18 CGGGCAAGTCAGAGCATTAGCAACT 55E4 V_(L)75 ATTTAAAT 49B11V_(L)75 50H10 V_(L)75 53C1 V_(L)75 56G1 V_(L)76 51C1 V_(L)95 60G5.1V_(L)74 52F8 1250 V_(L)42 CDRL1-19 AGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGAT 52H2 1251 V_(L)84 CDRL1-20AGGGCCAGTCAGAGTGTTAGAAGCA GCTACTTAGCC 53F6 1252 V_(L)63 CDRL1-21AGGTCTAGTCAGAGCCTCCAGCATAG TAATGGATACAACTATTTGGAT 53H5.2 1253 V_(L)62CDRL1-22 CGGGCAAGTCAGGGCATTAGAAATG 50G5 v1 V_(L)93 ATTTAGGC 53H5.3 1254V_(L)80 CDRL1-23 AGGGCCAGTCAGAGTGTTAGCAGCA ACGTCGCC 54A1 1255 V_(L)44CDRL1-24 CAGGCGAGTCAGGACATTAGCATCTA 55G9 V_(L)44 TTTAAAT 54H10.1 1256V_(L)53 CDRL1-25 AGGGCCAGTCAGAGTTTTAGCAGCA 55D1 V_(L)53 GTTACTTAGCC 48H3V_(L)53 53C11 V_(L)53 55D3 1257 V_(L)71 CDRL1-26CGGGCGAGTCAGGACATTAGCAATT 50D4 V_(L)92 ATTTAGCC 55E9 1258 V_(L)68CDRL1-27 AGGTCTAGTCAGAGCCTCCTGCATAG TAACGGATTCAACTATTTGGAT 55G5 1259V_(L)83 CDRL1-28 TCTGGAGACGAATTGGGGGATAAAT ATGCTTGC 56A7 1260 V_(L)52CDRL1-29 CGGGCGAGTCAGGATATTAGCAGTTG 56E4 V_(L)52 GTTAGCC 56C11 1261V_(L)64 CDRL1-30 GGGGGAAACGACATTGGAAGTAAAA GTGTGCAC 56E7 1262 V_(L)86CDRL1-31 CAGGCGAGTCAGGACATTAAAAAAT TTTTAAAT 56G3.2 1263 V_(L)85 CDRL1-32CAGGGCCAGGCAGAGTGTTGGCAGT AACTTAATC 56G3.3 1264 V_(L)81 CDRL1-33AGGGCCAGTCAGAGTGTTAGCAGAG 55B10 V_(L)81 ACTACTTAGCC 61H5 V_(L)88 52B957B12 1265 V_(L)72 CDRL1-34 CGGGCGAGTCATGACATTAGCAATTA TTTAGCC 57D9 1266V_(L)87 CDRL1-35 AGGGCCAGTCCGAGTGTTAGCAGCA GCTACTTAGCC 53C3.2 1267V_(L)96 CDRL1-36 AGGGCCAGTCAGAGTATTAGCAGCA ATTTAGCC 59C9 1268 V_(L)50CDRL1-37 CGGGCGAGTCAGGATATTGACAGCT 58A5 V_(L)50 GGTTAGTC 57A4 V_(L)5057F9 V_(L)50 59D10 1269 V_(L)56 CDRL1-38 TCTGGAGATGCAGTGCCAAAAAAAT v1ATGCTAAT 59D10 1270 V_(L)57 CDRL1-39 TCTGGAGATAATTTGGGGGATAAATA v2V_(L)27 TGCTTGC 65D1 59G10.2 1271 V_(L)60 CDRL1-40TCTGGAGATAATTTGGGGGATAAATA TGCTTTC 59G10.3 1272 V_(L)54 CDRL1-41TCTGGAAGCAGCTCCAACATTGGGGA TAATTATGTATCC 54H10.3 1273 V_(L)97 CDRL1-42CGGGCAAGTCAGACCATTAGCATCTA TTTAAAT 60F9 1274 V_(L)58 CDRL1-43AGGGCCAGTCAGAGGGTTCCCAGCA 48B4 V_(L)58 GCTACATAGTC 52D6 V_(L)58 60G5.21275 V_(L)46 CDRL1-44 TCTGGAAATAAATTGGGGGATAAAT ATGTTTGC 61G5 1276V_(L)59 CDRL1-45 AGGGCCAGTCAGAGAGTTCCCAGCA GCTACTTAGTC 64E6 1277 V_(L)3CDRL1-46 AGGGCCAGTCAGAGTGTTAGGAACA 65E8 V_(L)3 GCTACTTAGCC 65F11 V_(L)367G7 V_(L)3 63H11 V_(L)3 66F6 V_(L)15 63B6 1278 V_(L)4 CDRL1-47AGGGCCAGTCAGAGTGTTAGTAACA 64D4 V_(L)4 GCTACTTAGCC 65C3 1279 V_(L)5CDRL1-48 AGGGCCAGTCAGAGTGTTAGCAGCC 68D5 V_(L)5 AGTTAGCC 63E6 1280 V_(L)6CDRL1-49 CGGACAAGTCAGAGTATTAGCAGCT ATTTAAAT 66F7 1281 V_(L)7 CDRL1-50CGGACAAGTCAGAGCATTAGCAACT ATTTAAAT 64H5 1282 V_(L)8 CDRL1-51GGGGGAAACAACATTGGAAGTAAAA 65G4 V_(L)8 ATGTACAC 65E3 V_(L)25 64H6 V_(L)3767G10 1283 V_(L)9 CDRL1-52 GGGGGAAACAACATTGGAAGTAAAG v1 CTGTGCAC 63A10V_(L)22 63A10v2 V_(L)101 67G10 1284 V_(L)10 CDRL1-53TCTGGAGATAAATTGGGGGATAAAT v2 ATGCTTGC 63F5 1285 V_(L)14 CDRL1-54AGGGCCAGTCAGACTGTTAGGAACA ACTACTTAGCC 64A7 1286 V_(L)17 CDRL1-55AGGGCCAGTCAGAGTGTTAGTCGCA ACTACTTAGCC 65C1 1287 V_(L)16 CDRL1-56AGGGCCAGTCAGACTATTAGGAACA GCTACTTAGCC 66B4 1288 V_(L)11 CDRL1-57CGGGCGAGTCAGGGTATTAGCAGGT GGTTAGCC 55A7 1289 V_(L)98 CDRL1-58CGGGCAAGTCAGAGCATTAGCAGCT ATTTAAAT 68G5 1290 V_(L)13 CDRL1-59GGGGGTAACAACATTGGAAGTATAA ATGTGCAC 66D4 1291 V_(L)18 CDRL1-60CGGGCAAGTCAGATCATTAGCAGGT ATTTAAAT 65B1 1292 V_(L)19 CDRL1-61CGGGCAAGTCAGAACATTAACAACT ATTTAAAT 67A4 1293 V_(L)20 CDRL1-62GGGGGAAACAACATTGGAAGTAAAA GTGTGCAC 65B4 1294 V_(L)21 CDRL1-63GGGGGAAACAACATTGGAAGTAAAA GTGTGCAG 55E6 1295 V_(L)99 CDRL1-64AGGGCCAGTCAGAGTGTTAGTCGCA GCCACTTAGCC 65H11 1296 V_(L)23 CDRL1-65GGGGGAAACAACATTGGAAGTAAAA CTGTGCAC 64C8 1297 V_(L)24 CDRL1-66AGGTCTAGTCCAAGCCTCGTATACAG TGATGGAAACACCTACTTGAAT 65D4 1298 V_(L)26CDRL1-67 GGGGGAAATGACATTGGAAGTAAAA ATGTGCAC 61E1 1299 V_(L)100 CDRL1-68CGGGCAAGTCAGAGCATTGGCACCTT TTTAAAT 67G8 1300 V_(L)28 CDRL1-69GGGGGAAACAACATTGGAAGTTACA ATGTGTTC 65B7 1301 V_(L)29 CDRL1-70AGGGCCAGTCAGAGTGTTAGCAGCA TGTACTTAGCC 64A6 1302 V_(L)30 CDRL1-71AGGGCCAGTCAGAGTGTTAACAGCA ACTTAGCC 65F9 1303 V_(L)31 CDRL1-72AGGGCCAGTCAGAGTGTTAGCAGCA 67F5 V_(L)32 ACTTAGCC 64B10 1304 V_(L)33CDRL1-73 TCTGGAAGCAGCTCCAATATTGGGAA TAATTATGTAGCC 68C8 1305 V_(L)34CDRL1-74 TCTGGAAGCAGTTCCAACATTGGAAA TAATTATGTATCC 67A5 1306 V_(L)35CDRL1-75 AGGTCTAGTCAGAGCCTCTTAAATAG 67C10 V_(L)36TGATGATGGAAATACCTATTTGGAC 63F9 1307 V_(L)38 CDRL1-76CGGGCAAGTCAGGACATTAGAAATG ATTTAGCC 67F6v1 1308 V_(L)39 CDRL1-77AGGTCTAGTCAGAGCCTCTTAAATAG 67F6v2 V_(L)39 TGATGCTGGTACCACCTATTTGGAC 50G5v2 1309 V_(L)94 CDRL1-78 AGGTCTAGTCAAAGACTCGTATACAGTGATGGAAACACCTACTTGAAT 48G4 1310 V_(L)89 CDRL1-79AGGGCCAGTCAGAGTGTTGCCAGCA 53C3.1 V_(L)89 GTTACTTAGTC 58C2 1311 V_(L)91CDRL1-81 AGGTCTAGTCAGAGCCTCTTCGATAA TGATGATGGAGACACCTATTTGGAC 65B7v11887 V_(L)29 CDRL1-82 AGGGCCAGTCAGAGTGTTAGCAGCA TCTACTTAGCC 65B7v2 1888V_(L)107 CDRL1-83 AGGTCTAGTCAAAGCCTCGTATACAG TGATGGAGACACCTACTTGAAT63G8v3 1889 V_(L)106 CDRL1-84 CGGGCAAGTCAGGGCATTAGAAGTG 63G8v2 V_(L)105GTTTAGGC 63A10v3 1890 V_(L)102 CDRL1-85 TCTGGAGATAAATTGGGGAATAGATATACTTGC 65H11v2 1891 V_(L)23 CDRL1-86 TCTGGAGATAAATTGGGGGATAGATATGTTTGT 48C9 1312 V_(L)78 CDRL2-1 GTTGCATCCAGTTTGGAAAGT 49A12 V_(L)7851E2 V_(L)78 48F3 1313 V_(L)77 CDRL2-2 GCTGTATCCAGTTTGCAAAGT 48F8 1314V_(L)49 CDRL2-3 TTTGCTTCCCAGTCCTTCTCA 53B9 V_(L)49 56B4 V_(L)49 57E7V_(L)49 57F11 V_(L)49 48H11 1315 V_(L)40 CDRL2-4 GGTGCATCTAATTTACAGAGT49A10 1316 V_(L)65 CDRL2-5 ACGCTTTCCTATCGGGCCTCT 48D4 V_(L)65 49G2V_(L)66 50C12 V_(L)66 55G11 V_(L)66 60D7 V_(L)69 67A5 V_(L)35 67C10V_(L)36 50G1 V_(L)90 60D7 V_(L)36 58C2 V_(L)91 49C8 1317 V_(L)45 CDRL2-6GATGTATCCAATTTGGAAACA 52H1 V_(L)45 54A1 V_(L)44 55G9 V_(L)44 49G3 1318V_(L)47 CDRL2-7 GATGCATCCAATTTGGAAACA 56E7 V_(L)86 49H12 1319 V_(L)43CDRL2-8 GATACATTCATTTTGGAAACA 51A8 1320 V_(L)61 CDRL2-9GAGGATAAAGAAAGATCCTCT 51C10.1 1321 V_(L)55 CDRL2-10GAGGACAGCAAACGACCCTCC 59D10 V_(L)56 v1 51C10.2 1322 V_(L)70 CDRL2-11CAAAATAACAAGCGGCCCTCA 59G10.2 V_(L)60 51E5 1323 V_(L)79 CDRL2-12GCTGCATCCAGTTTGCAATTT 51G2 1324 V_(L)51 CDRL2-13 GATGCATCCAGTTTGCAAAGT52A8 1325 V_(L)41 CDRL2-14 GCTGCATCCAGTTTGCAAAGT 52C5 V_(L)73 53H5.2V_(L)62 55D3 V_(L)71 56G1 V_(L)76 57B12 V_(L)72 63E6 V_(L)6 66F7 V_(L)766D4 V_(L)18 50G5 v1 V_(L)93 51C1 V_(L)95 55A7 V_(L)98 61E1 V_(L)10060G5.1 V_(L)74 52B8 1326 V_(L)82 CDRL2-15 GGTGCATCCACCAGGGCCACT 53H5.3V_(L)80 65F9 V_(L)31 52C1 1327 V_(L)67 CDRL2-16 GACAATAATAAGCGACCCTCA59G10.3 V_(L)54 68C8 V_(L)34 52F8 1328 V_(L)42 CDRL2-17TTGGGTTCTAATCGGGCCTCC 55E9 V_(L)68 52H2 1329 V_(L)84 CDRL2-18GGTGCATCCAGGAGGGCCACT 53F6 1330 V_(L)63 CDRL2-19 TTGGATTCTAATCGGGCCTCC54H10.1 1331 V_(L)53 CDRL2-20 GGTGCATCCAGCAGGGCCACT 55D1 V_(L)53 48H3V_(L)53 53C11 V_(L)53 57D9 V_(L)87 61H5 V_(L)88 52B9 V_(L)88 63F5V_(L)14 64A7 V_(L)17 65B7v1 V_(L)29 55E6 V_(L)99 55E4 1332 V_(L)75CDRL2-21 ACAGCTTCCAGTTTGCAAAGT 49BG11 V_(L)75 50H10 V_(L)75 53C1 V_(L)7550G5v2 1333 V_(L)94 CDRL2-22 AAGGTTTCTAACTGGGACTCT 65B7v2 V_(L)107 55G51334 V_(L)83 CDRL2-23 CAAGATACCAAGCGGCCCTCA 56A7 1335 V_(L)52 CDRL2-24GATGCATCCACTTTGCAAAGT 56E4 V_(L)52 56C11 1336 V_(L)64 CDRL2-25GATGATAGCGACCGGCCCTCA 67A4 V_(L)20 65B4 V_(L)21 56G3.2 1337 V_(L)85CDRL2-26 GGTGCATCCAGCAGGGACACT 56G3.3 1338 V_(L)81 CDRL2-27GGTGCATCCGCCAGGGCCACT 55B10 V_(L)81 59A10 1339 V_(L)48 CDRL2-28GGTGCATCCAGTTTGCAAAGT 49H4 V_(L)48 59C9 1340 V_(L)50 CDRL2-29GCTGCATCCAATTTGCAAAGA 58A5 V_(L)50 57A4 V_(L)50 57F9 V_(L)50 63G8v1V_(L)104 63GBv2 V_(L)105 63G8v3 V_(L)106 64A8 V_(L)1 67B4 V_(L)1 68D3V_(L)1 59D10 1341 V_(L)57 CDRL2-30 CAAGATACCAAGCGGCCCTCA v2 60F9 1342V_(L)58 CDRL2-31 GGTTCATCCAACAGGGCCACT 48B4 V_(L)58 52D6 V_(L)58 60G5.21343 V_(L)46 CDRL2-32 CAAGATAGCAAGCGGCCCTCA 65D1 V_(L)27 65H11v2V_(L)103 61G5 1344 V_(L)59 CDRL2-33 GGTGCATCCAACAGGGCCACA 64E6 1345V_(L)3 CDRL2-34 GGTGCATTTAGCAGGGCCTCT 65E8 V_(L)3 65F11 V_(L)3 67G7V_(L)3 63H11 V_(L)3 63B6 1346 V_(L)4 CDRL2-35 GGTGCATTCAGTAGGGCCACT 64D4V_(L)4 65C1 V_(L)16 66F6 V_(L)15 48G4 V_(L)83 53C3.1 V_(L)83 65C3 1347V_(L)5 CDRL2-36 GGTGCCTCCAACAGGGCCATT 68D5 V_(L)5 64H5 1348 V_(L)8CDRL2-37 AGGGATAGCAAGCGGCCCTCT 65G4 V_(L)8 67G8 V_(L)28 64H6 V_(L)3767G10 1349 V_(L)9 CDRL2-38 AGCGATAGCAACCGGCCCTCA v1 65H11 V_(L)23 67G101350 V_(L)10 CDRL2-39 CAAGATAACGAGCGGCCCTCA v2 66B4 1351 V_(L)11CDRL2-40 GCTGCATCCAGTTTGAAAAGT 66G2 1352 V_(L)12 CDRL2-41GCTGCATCCAATTTGCAAAGT 68G5 1353 V_(L)13 CDRL2-42 AGGGATAGGAACCGGCCCTCT65E3 V_(L)25 65D4 V_(L)26 65B1 1354 V_(L)19 CDRL2-43ACTACATCCAGTTTGCAAAGT 53C3.2 1355 V_(L)96 CDRL2-44 GGTACATCCATCAGGGCCAGT63A10v1 1356 V_(L)22 CDRL2-45 TGTGATAGCAACCGGCCCTCA 63A10v2 V_(L)10154H10.3 1357 V_(L)97 CDRL2-46 TCTGCATCCAGTTTGCAAAGT 64C8 1358 V_(L)24CDRL2-47 AAGGGTTCTAACTGGGACTCA 64A6 1359 V_(L)30 CDRL2-48GGTACATCCACCAGGGCCACT 67F5 1360 V_(L)32 CDRL2-49 GGTTCATCCAACAGGGCCATT64B10 1361 V_(L)33 CDRL2-50 GACAATGATAAGCGACCCTCA 63F9 1362 V_(L)38CDRL2-51 GCTTCATCCAGTTTGCAAAGT 67F6v2 1363 V_(L)39 CDRL2-52ACGCTTTCCTTTCGGGCCTCT 50D4 1364 V_(L)92 CDRL2-53 GCTGCATCCACTTTGCTATCA68A10v3 1892 V_(L)102 CDRL2-54 CAAGATAGCGAGCGGCCCTCA 48C9 1365 V_(L)78CDRL3-1 CAACAGAGTGACAGTATCCCTCGGACG 49A12 51E2 48F3 1366 V_(L)77 CDRL3-2CAACAGAGTTACAGTGCTACATTCACT 48F8 1367 V_(L)49 CDRL3-3CATCAGAGTAGTGATTTACCGCTCACT 53B9 V_(L)49 56B4 V_(L)49 57E7 V_(L)49 57F11V_(L)49 48H11 1368 V_(L)40 CDRL3-4 CAACAGAGTTACAATACCCCGTGCAGT 49A101369 V_(L)65 CDRL3-5 ATGCAACGTATAGAGTTTCCGATCACC 48D4 V_(L)65 67F6v2V_(L)108 49C8 1370 V_(L)45 CDRL3-6 CAACAATATGATAATCTCCCATTCACT 52H1V_(L)45 67C10 V_(L)36 67F6v1 V_(L)39 49G2 1371 V_(L)66 CDRL3-7ATGCAACATATAGAATTTCCTTCGACC 50C12 V_(L)66 55G11 V_(L)66 49G3 1372V_(L)47 CDRL3-8 CACCAGTATGATGATCTCCCGCTCACT 49H12 1373 V_(L)43 CDRL3-9CAACAGTATGACAATTTACCGCTCACC 54A1 V_(L)44 55G9 V_(L)44 51A8 1374 V_(L)61CDRL3-10 CAGTCTTATGATCGCAACAATCATGT GGTT 51C10.1 1375 V_(L)55 CDRL3-11TACTCAACAGACAGCAGTGTTAATCA TGTGGTA 51C10.2 1376 V_(L)70 CDRL3-12CAGGCGTGGGATAGTAGTACTGCGGTA 51E5 1377 V_(L)79 CDRL3-13CTACAACATAGTAGTTACCCGCTCACT 51G2 1378 V_(L)51 CDRL3-14CAACAGACTAACAGTTTCCCTCCGTG 56A7 V_(L)52 GACG 56E4 V_(L)52 59A10 V_(L)4849H4 V_(L)48 59C9 V_(L)50 58A5 V_(L)50 57A4 V_(L)50 57F9 V_(L)50 52A81379 V_(L)41 CDRL3-15 CAGCAGAGTTACAGTACCCCGCTCACT 65B1 V_(L)19 52B8 1380V_(L)82 CDRL3-16 CAGCAGTATAATAACTGGCCGCTCACT 56G3.2 V_(L)85 52C1 1381V_(L)67 CDRL3-17 GGAACATGGGATAGCAGCCTGAGTG 64B10 V_(L)33 CTGTGGTA 68C8V_(L)34 52C5 1382 V_(L)73 CDRL3-18 CAACAGAGTTCCAGTATCCCTTGGACG 55E4V_(L)75 49B11 V_(L)75 50H10 V_(L)75 53C1 V_(L)75 51C1 V_(L)95 60G5.1V_(L)74 52F8 1383 V_(L)42 CDRL3-19 ATGCAAGCTCTACAAACTCCATTCACT 52H2 1384V_(L)84 CDRL3-20 CAGCAGTATGGTAGTTCACCTCGCAGT 53F6 1385 V_(L)63 CDRL3-21ATGCAAGGTCTACAAACTCCTCCCACT 53H5.2 1386 V_(L)62 CDRL3-22CTACAGCATAAGAGTTACCCATTCACT 53H5.3 1387 V_(L)80 CDRL3-23CAGCAGTTTAGTAACTCAATCACC 54H10.1 1388 V_(L)53 CDRL3-24CAGCAGTATGGTAGCTCACGGACG 55D1 V_(L)53 48H3 V_(L)53 53C11 V_(L)53 55D31389 V_(L)71 CDRL3-25 CAACAGTATAATATTTACCCTCGGACG 55E9 1390 V_(L)68CDRL3-26 ATGCAAGCTCTACAAACTCTCATCACC 55G5 1391 V_(L)83 CDRL3-27CAGGCGTGGGACAGCGGCACTGTGG TA 56C11 1392 V_(L)64 CDRL3-28CAGGTGTGGGATAGTAGTAGTGATGT GGTA 56E7 1393 V_(L)86 CDRL3-29CAACAATATGCTATTCTCCCATTCACT 56G1 1394 V_(L)76 CDRL3-30CAACAGAGTTCCACTATCCCTTGGACG 56G3.3 1395 V_(L)81 CDRL3-31CAGCAATATGGTAGATCACTATTCACT 55B10 V_(L)81 61H5 V_(L)88 52B9 V_(L)8857B12 1396 V_(L)72 CDRL3-32 CAACAATATAATACTTACCCTCGGACG 57D9 1397V_(L)87 CDRL3-33 CATCAGTATGGTACCTCACCGTGCAGT 59D10 1398 V_(L)56 CDRL3-34TACTCAACAGACAGCAGTGGTAATCA v1 TGTGGTA 59D10 1399 V_(L)57 CDRL3-35CAGGCGTGGGACAGCAGCACTACAT v2 GGGTG 59G10.2 1400 V_(L)60 CDRL3-36CAGGCGTGGGACAGCGCCACTGTGA TT 59G10.3 1401 V_(L)54 CDRL3-37GGAACATGGGACAGCAGCCTGAGTG TTATGGTT 60D7 1402 V_(L)69 CDRL3-38ATGCAACGTATAGAGTTTCCGCTCACT 50G1 V_(L)90 60F9 1403 V_(L)58 CDRL3-39CAGCAGTATGGTAGCTCACCTCCGTG 48B4 V_(L)58 GACG 52D6 V_(L)58 61G5 V_(L)5960G5.2 1404 V_(L)46 CDRL3-40 CAGGCGTGGGACAGCAGCACTTGGG TG 63G8v1 1405V_(L)104 CDRL3-41 CTCCAGCATAATAGTTACCCTCTCACT 63G8v2 V_(L)105 64A8V_(L)1 67B4 V_(L)1 68D3 V_(L)2 64E6 1406 V_(L)3 CDRL3-42CAGCAGTTTGGAAGCTCACTCACT 65E8 V_(L)3 65F11 V_(L)3 67G7 V_(L)3 63H11V_(L) 63F5 V_(L)14 65C1 V_(L)16 66F6 V_(L)15 63B6 1407 V_(L)4 CDRL3-43CAGCAGTTTGGTAGGTCATTCACT 64D4 V_(L)4 65C3 1408 V_(L)5 CDRL3-44CAGCAGTATAATAACTGGCCGTGGACG 68D5 V_(L)5 63E6 1409 V_(L)6 CDRL3-45CAACAGAGTTACAGTACCTCGCTCACT 66F7 V_(L)7 64H5 1410 V_(L)8 CDRL3-46CAGGTGTGGGACAGCAGTAGTGTGG 65G4 V_(L)8 TA 67G10 1411 V_(L)9 CDRL3-47CAGGTGTGGGACAGTAGTAGTGATG v1 GGGTA 67G10 1412 V_(L)10 CDRL3-48CAGGCGTGGGACAGCACCACTGTGG v2 TA 63A10v2 V_(L)101 63A10v3 V_(L)102 64A71413 V_(L)17 CDRL3-49 CAGCAGTATGGTAGTTCATCTCTGTG CAGT 66B4 1414 V_(L)11CDRL3-50 CAACAGGCTAACAGTTTCCCTCCGACG 66G2 1415 V_(L)12 CDRL3-51CTACAACTTAATGGTTACCCTCTCACT 68G5 1416 V_(L)13 CDRL3-52CAGTTGTGGGACAGCAGCACTGTGGTT 66D4 1417 V_(L)18 CDRL3-53CAACAGAGTTACAGTTCCCCGCTCACT 54H10.3 V_(L)97 55A7 1418 V_(L)98 CDRL3-54CAACAGACTTACAGTGCCCCATTCACT 67A4 1419 V_(L)20 CDRL3-55CAGGTGTGGGATAGTAGTAGTGATCA 65B4 V_(L)21 TGTGGTA 63A10 1420 V_(L)22CDRL3-56 CATGCGTGTGGGAGCAGTAGTAGCG ATGGGGTA 65H11 1421 V_(L)23 CDRL3-57CAGGTGTGGGACAGTAGTTGTGATGG GGTA 64C8 1422 V_(L)24 CDRL3-58ATACAAGATACACACTGGCCCACGTG CAGT 65E3 1423 V_(L)25 CDRL3-59CAGGTGTGGGACAGCAGCACTGTGG 67G8 V_(L)28 TC 65D4 1424 V_(L)26 CDRL3-60CAGGTGTGGGACAGCAACCCTGTGGTA 65D1 1425 V_(L)27 CDRL3-61CAGGCGTGGGACAGCAGGGTA 65B7v1 1426 V_(L)29 CDRL3-62CAGCAGTATGGTAGCTCGTGCAGT 64A6 1427 V_(L)30 CDRL3-63CAGCAATATAATACCTGGCCGTGGACG 65F9 V_(L)31 67F5 1428 V_(L)32 CDRL3-64CAGCAGTATGAAATTTGGCCGTGGACG 55E6 1429 V_(L)99 CDRL3-65CAGCAGTATGGTAGTTCACCGTGGACG 67A5 1430 V_(L)35 CDRL3-66ATGCAACGTCTAGAGTTTCCTATTACC 58C2 V_(L)91 61E1 1431 V_(L)100 CDRL3-67CAACAGAGTTTCAGTACCCCGCTCACT 64H6 1432 V_(L)37 CDRL3-68CAGGTGTGGGACAGCAGTCCTGTGGTA 63F9 1433 V_(L)38 CDRL3-69CTACAGCGTAATAGTTACCCGCTCACT 53C3.2 1434 V_(L)96 CDRL3-70CACCAGTATACTAACTGGCCTCGGACG 48G4 1435 V_(L)89 CDRL3-71CAGCAGTATGGTACCTCACCATTTACT 53C3.1 V_(L)89 50G5 v1 1436 V_(L)93 CDRL3-72CTACAGCATAATAGTTACCCTCGGACG 64B10v2 1893 V_(L)33 CDRL3-73TATAGCAGCACCTGGGACTACTATTA CGGTGTGGACGTC 50D4 1437 V_(L)92 CDRL3-74CAAAAGTATTACAGTGCCCCTTTCACT 50G5 v2 1438 V_(L)94 CDRL3-75ATGGAAGGTACACACTGGCCTCGGG AC 63G8v3 1894 V_(L)106 CDRL3-76CTCCAACATAATACTTACCCTCTCACT 65B7v2 1895 V_(L)107 CDRL3-77ATGCAAGGTACACACTGGCGGGGTT GGACG 65H11v2 1896 V_(L)103 CDRL3-78CAGGCGTGGGACAGCATCACTGTGGTA 63A10v1 1897 V_(H)21 CDRL3-79CAGGTGTGGGACAGTAGTAGTGATG GGGTA

The structure and properties of CDRs within a naturally occurringantibody has been described, supra. Briefly, in a traditional antibody,the CDRs are embedded within a framework in the heavy and light chainvariable region where they constitute the regions responsible forantigen binding and recognition. A variable region comprises at leastthree heavy or light chain CDRs, see, e.g., Kabat et al., (1991)“Sequences of Proteins of Immunological Interest”, 5th Ed., US Dept. ofHealth and Human Services, PHS, NIH, NIH Publication no. 91-3242; seealso Chothia and Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al.,(1989) Nature 342: 877-883), within a framework region (designatedframework regions 1-4, FR1, FR2, FR3, and FR4, by Kabat et al., (1991);see also Chothia and Lesk, (1987) supra). The CDRs provided herein,however, can not only be used to define the antigen binding domain of atraditional antibody structure, but can be embedded in a variety ofother polypeptide structures, as described herein.

In one aspect, the CDRs provided are (a) a CDRH selected from the groupconsisting of (i) a CDRH1 selected from the group consisting of SEQ IDNOS 603-655; (ii) a CDRH2 selected from the group consisting of SEQ IDNOS 656-732; (iii) a CDRH3 selected from the group consisting of SEQ IDNOS 733-813; and (iv) a CDRH of (i), (ii) and (iii) that contains one ormore amino acid substitutions, deletions or insertions of no more thanfive, four, three, two, or one amino acids; (B) a CDRL selected from thegroup consisting of (i) a CDRL1 selected from the group consisting ofSEQ ID NOS 814-893; (ii) a CDRL2 selected from the group consisting ofSEQ ID NOS 894-946; (iii) a CDRL3 selected from the group consisting ofSEQ ID NOS 947-1020; and (iv) a CDRL of (i), (ii) and (iii) thatcontains one or more amino acid substitutions, deletions or insertionsof no more than 1, 2, 3, 4, or 5 amino acids amino acids.

In another aspect, an antigen binding protein comprises 1, 2, 3, 4, 5,or 6 variant forms of the CDRs listed in Tables 3A and 3B, infra, eachhaving at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequenceidentity to a CDR sequence listed in Tables 3A and 3B, infra. Someantigen binding proteins comprise 1, 2, 3, 4, 5, or 6 of the CDRs listedin Tables 3A and 3B, infra, each differing by no more than 1, 2, 3, 4 or5 amino acids from the CDRs listed in these tables.

In still another aspect, an antigen binding protein includes thefollowing associations of CDRL1, CDRL2 and CDRL3, presented forconvenience in tabular form and in reference to the clone source of theassociation:

TABLE 4 CDRL Associations Clone ID CDRL1 CDRL2 CDRL3 63G8 CDRL1-13CDRL2-29 CDRL3-41 64A8 CDRL1-13 CDRL2-29 CDRL3-41 67B4 CDRL1-13 CDRL2-29CDRL3-41 68D3 CDRL1-13 CDRL2-29 CDRL3-41 64E6 CDRL1-46 CDRL2-34 CDRL3-4265E8 CDRL1-46 CDRL2-34 CDRL3-42 65F11 CDRL1-46 CDRL2-34 CDRL3-42 67G7CDRL1-46 CDRL2-34 CDRL3-42 63B6 CDRL1-47 CDRL2-3 CDRL3-43 64D4 CDRL1-47CDRL2-3 CDRL3-43 65C3 CDRL1-48 CDRL2-36 CDRL3-44 68D5 CDRL1-48 CDRL2-36CDRL3-44 63E6 CDRL1-49 CDRL2-14 CDRL3-45 66F7 CDRL1-50 CDRL2-14 CDRL3-4564H5 CDRL1-51 CDRL2-37 CDRL3-46 65G4 CDRL1-51 CDRL2-37 CDRL3-46 67G10v1CDRL1-52 CDRL2-38 CDRL3-47 67G10v2 CDRL1-53 CDRL2-39 CDRL3-48 66B4CDRL1-57 CDRL2-40 CDRL3-50 66G2 CDRL1-22 CDRL2-41 CDRL3-51 68G5 CDRL1-59CDRL2-42 CDRL3-52 63F5 CDRL1-54 CDRL2-20 CDRL3-42 66F6 CDRL1-46 CDRL2-35CDRL3-42 65C1 CDRL1-56 CDRL2-35 CDRL3-42 64A7 CDRL1-55 CDRL2-20 CDRL3-4966D4 CDRL1-60 CDRL2-14 CDRL3-53 65B1 CDRL1-61 CDRL2-43 CDRL3-15 67A4CDRL1-62 CDRL2-25 CDRL3-55 65B4 CDRL1-63 CDRL2-25 CDRL3-55 63A10CDRL1-52 CDRL2-45 CDRL3-56 65H11 CDRL1-65 CDRL2-38 CDRL3-57 64C8CDRL1-66 CDRL2-47 CDRL3-58 65E3 CDRL1-51 CDRL2-42 CDRL3-59 65D4 CDRL1-67CDRL2-42 CDRL3-60 65D1 CDRL1-39 CDRL2-32 CDRL3-61 67G8 CDRL1-69 CDRL2-37CDRL3-59 65B7 CDRL1-70 CDRL2-20 CDRL3-62 64A6 CDRL1-71 CDRL2-48 CDRL3-6365F9 CDRL1-72 CDRL2-15 CDRL3-63 67F5 CDRL1-72 CDRL2-49 CDRL3-64 64B10CDRL1-73 CDRL2-50 CDRL3-17 68C8 CDRL1-74 CDRL2-16 CDRL3-17 67A5 CDRL1-75CDRL2-5 CDRL3-66 67C10 CDRL1-75 CDRL2-5 CDRL3-5 64H6 CDRL1-51 CDRL2-37CDRL3-68 63F9 CDRL1-76 CDRL2-51 CDRL3-69 67F6 CDRL1-77 CDRL2-52 CDRL3-548H11 CDRL1-4 CDRL2-4 CDRL3-4 52A8 CDRL1-15 CDRL2-14 CDRL3-15 52F8CDRL1-19 CDRL2-17 CDRL3-19 49H12 CDRL1-9 CDRL2-8 CDRL3-9 54A1 CDRL1-24CDRL2-6 CDRL3-9 55G9 CDRL1-24 CDRL2-6 CDRL3-9 49C8 CDRL1-6 CDRL2-6CDRL3-6 52H1 CDRL1-6 CDRL2-6 CDRL3-6 60G5.2 CDRL1-44 CDRL2-32 CDRL3-4049G3 CDRL1-8 CDRL2-7 CDRL3-8 59A10 CDRL1-14 CDRL2-28 CDRL3-14 49H4CDRL1-14 CDRL2-28 CDRL3-14 48F8 CDRL1-3 CDRL2-3 CDRL3-3 53B9 CDRL1-3CDRL2-3 CDRL3-3 56B4 CDRL1-3 CDRL2-3 CDRL3-3 57E7 CDRL1-3 CDRL2-3CDRL3-3 57F11 CDRL1-3 CDRL2-3 CDRL3-3 59C9 CDRL1-37 CDRL2-29 CDRL3-1458A5 CDRL1-37 CDRL2-29 CDRL3-14 57A4 CDRL1-37 CDRL2-29 CDRL3-14 57F9CDRL1-37 CDRL2-29 CDRL3-14 51G2 CDRL1-14 CDRL2-13 CDRL3-14 56A7 CDRL1-29CDRL2-24 CDRL3-14 56E4 CDRL1-29 CDRL2-24 CDRL3-14 54H10.1 CDRL1-25CDRL2-20 CDRL3-24 55D1 CDRL1-25 CDRL2-20 CDRL3-24 48H3 CDRL1-25 CDRL2-20CDRL3-24 53C11 CDRL1-25 CDRL2-20 CDRL3-24 59G10.3 CDRL1-41 CDRL2-16CDRL3-37 51C10.1 CDRL1-12 CDRL2-10 CDRL3-11 59D10 v1 CDRL1-38 CDRL2-10CDRL3-34 59D10 v2 CDRL1-39 CDRL2-30 CDRL3-35 60F9 CDRL1-43 CDRL2-31CDRL3-39 48B4 CDRL1-43 CDRL2-31 CDRL3-39 52D6 CDRL1-43 CDRL2-31 CDRL3-3961G5 CDRL1-45 CDRL2-33 CDRL3-39 59G10.2 CDRL1-40 CDRL2-11 CDRL3-36 51A8CDRL1-10 CDRL2-9 CDRL3-10 53H5.2 CDRL1-22 CDRL2-14 CDRL3-22 53F6CDRL1-21 CDRL2-19 CDRL3-21 56C11 CDRL1-30 CDRL2-25 CDRL3-28 49A10CDRL1-5 CDRL2-5 CDRL3-5 48D4 CDRL1-5 CDRL2-5 CDRL3-5 49G2 CDRL1-7CDRL2-5 CDRL3-7 50C12 CDRL1-7 CDRL2-5 CDRL3-7 55G11 CDRL1-7 CDRL2-5CDRL3-7 52C1 CDRL1-17 CDRL2-16 CDRL3-17 55E9 CDRL1-27 CDRL2-17 CDRL3-2660D7 CDRL1-1 CDRL2-5 CDRL3-38 51C10.2 CDRL1-12 CDRL2-11 CDRL3-12 55D3CDRL1-26 CDRL2-14 CDRL3-25 57B12 CDRL1-34 CDRL2-14 CDRL3-32 52C5CDRL1-18 CDRL2-14 CDRL3-18 55E4 CDRL1-18 CDRL2-21 CDRL3-18 49B11CDRL1-18 CDRL2-21 CDRL3-18 50H10 CDRL1-18 CDRL2-21 CDRL3-18 53C1CDRL1-18 CDRL2-21 CDRL3-18 56G1 CDRL1-18 CDRL2-14 CDRL3-30 48F3 CDRL1-2CDRL2-2 CDRL3-2 48C9 CDRL1-1 CDRL2-1 CDRL3-1 49A12 CDRL1-1 CDRL2-1CDRL3-1 51E2 CDRL1-1 CDRL2-1 CDRL3-1 51E5 CDRL1-13 CDRL2-12 CDRL3-1353H5.3 CDRL1-23 CDRL2-15 CDRL3-23 56G3.3 CDRL1-33 CDRL2-27 CDRL3-3155B10 CDRL1-33 CDRL2-27 CDRL3-31 52B8 CDRL1-16 CDRL2-15 CDRL3-16 55G5CDRL1-28 CDRL2-23 CDRL3-27 52H2 CDRL1-20 CDRL2-18 CDRL3-20 56G3.2CDRL1-32 CDRL2-26 CDRL3-16 56E7 CDRL1-31 CDRL2-7 CDRL3-29 57D9 CDRL1-35CDRL2-20 CDRL3-33 61H5 CDRL1-33 CDRL2-20 CDRL3-31 52B9 CDRL1-33 CDRL2-20CDRL3-31 48G4 CDRL1-79 CDRL2-35 CDRL3-71 53C3.1 CDRL1-79 CDRL2-35CDRL3-71 50G1 CDRL1-7 CDRL2-5 CDRL3-38 58C2 CDRL1-81 CDRL2-5 CDRL3-6660G5.1 CDRL1-18 CDRL2-14 CDRL3-18 54H10.3 CDRL1-42 CDRL2-46 CDRL3-5350G5 v1 CDRL1-22 CDRL2-14 CDRL3-72 50G5 v2 CDRL1-78 CDRL2-22 CDRL3-7551C1 CDRL1-18 CDRL2-14 CDRL3-18 53C3.2 CDRL1-36 CDRL2-44 CDRL3-70 50D4CDRL1-26 CDRL2-53 CDRL3-74 55A7 CDRL1-58 CDRL2-14 CDRL3-54 55E6 CDRL1-64CDRL2-20 CDRL3-65 61E1 CDRL1-68 CDRL2-14 CDRL3-67 63H11 CDRL1-46CDRL2-34 CDRL3-42

In an additional aspect, an antigen binding protein includes thefollowing associations of CDRH1, CDRH2 and CDRH3, presented forconvenience in tablular form and in reference to the clone source of theassociation:

TABLE 5 CDRH Associations Clone ID CDRH1 CDRH2 CDRH3 63G8 CDRH1-34CDRH2-12 CDRH3-50 64A8 CDRH1-34 CDRH2-12 CDRH3-50 67B4 CDRH1-34 CDRH2-12CDRH3-50 68D3 CDRH1-34 CDRH2-12 CDRH3-50 64E6 CDRH1-35 CDRH2-44 CDRH3-5165E8 CDRH1-35 CDRH2-44 CDRH3-51 65F11 CDRH1-35 CDRH2-44 CDRH3-51 67G7CDRH1-35 CDRH2-44 CDRH3-51 63B6 CDRH1-36 CDRH2-45 CDRH3-52 64D4 CDRH1-36CDRH2-45 CDRH3-52 65C3 CDRH1-24 CDRH2-46 CDRH3-53 68D5 CDRH1-24 CDRH2-46CDRH3-53 63E6 CDRH1-37 CDRH2-47 CDRH3-54 66F7 CDRH1-37 CDRH2-47 CDRH3-5464H5 CDRH1-12 CDRH2-48 CDRH3-55 65G4 CDRH1-12 CDRH2-48 CDRH3-55 67G10v1CDRH1-38 CDRH2-49 CDRH3-56 67G10v2 CDRH1-38 CDRH2-49 CDRH3-56 66B4CDRH1-15 CDRH2-53 CDRH3-59 66G2 CDRH1-12 CDRH2-54 CDRH3-50 68G5 CDRH1-12CDRH2-55 CDRH3-60 63F5 CDRH1-35 CDRH2-50 CDRH3-51 66F6 CDRH1-35 CDRH2-34CDRH3-51 65C1 CDRH1-35 CDRH2-52 CDRH3-58 64A7 CDRH1-40 CDRH2-51 CDRH3-5766D4 CDRH1-43 CDRH2-56 CDRH3-61 65B1 CDRH1-44 CDRH2-57 CDRH3-62 67A4CDRH1-45 CDRH2-58 CDRH3-63 65B4 CDRH1-46 CDRH2-59 CDRH3-64 63A10CDRH1-38 CDRH2-60 CDRH3-56 65H11 CDRH1-38 CDRH2-61 CDRH3-56 64C8CDRH1-12 CDRH2-62 CDRH3-65 65E3 CDRH1-47 CDRH2-63 CDRH3-66 65D4 CDRH1-48CDRH2-22 CDRH3-67 65D1 CDRH1-49 CDRH2-64 CDRH3-68 67G8 CDRH1-12 CDRH2-65CDRH3-69 65B7 CDRH1-50 CDRH2-52 CDRH3-70 64A6 CDRH1-14 CDRH2-66 CDRH3-7165F9 CDRH1-36 CDRH2-34 CDRH3-72 67F5 CDRH1-24 CDRH2-67 CDRH3-53 64B10CDRH1-36 CDRH2-68 CDRH3-73 68C8 CDRH1-51 CDRH2-69 CDRH3-74 67A5 CDRH1-25CDRH2-31 CDRH3-75 67C10 CDRH1-25 CDRH2-31 CDRH3-76 64H6 CDRH1-25CDRH2-70 CDRH3-77 63F9 CDRH1-52 CDRH2-71 CDRH3-78 67F6 CDRH1-53 CDRH2-31CDRH3-79 48H11 CDRH1-4 CDRH2-4 CDRH3-4 52A8 CDRH1-15 CDRH2-17 CDRH3-1752F8 CDRH1-17 CDRH2-20 CDRH3-21 49H12 CDRH1-10 CDRH2-10 CDRH3-10 54A1CDRH1-10 CDRH2-25 CDRH3-10 55G9 CDRH1-10 CDRH2-25 CDRH3-10 49C8 CDRH1-7CDRH2-7 CDRH3-7 52H1 CDRH1-7 CDRH2-7 CDRH3-7 60G5.2 CDRH1-33 CDRH2-42CDRH3-48 49G3 CDRH1-9 CDRH2-9 CDRH3-9 59A10 CDRH1-30 CDRH2-37 CDRH3-4149H4 CDRH1-30 CDRH2-37 CDRH3-41 48F8 CDRH1-3 CDRH2-3 CDRH3-3 53B9CDRH1-3 CDRH2-3 CDRH3-3 56B4 CDRH1-3 CDRH2-3 CDRH3-3 57E7 CDRH1-3CDRH2-3 CDRH3-3 57F11 CDRH1-3 CDRH2-3 CDRH3-3 59C9 CDRH1-31 CDRH2-38CDRH3-42 58A5 CDRH1-31 CDRH2-38 CDRH3-42 57A4 CDRH1-31 CDRH2-38 CDRH3-4257F9 CDRH1-31 CDRH2-38 CDRH3-42 51G2 CDRH1-3 CDRH2-16 CDRH3-16 56A7CDRH1-3 CDRH2-16 CDRH3-32 56E4 CDRH1-3 CDRH2-16 CDRH3-32 54H10.1CDRH1-21 CDRH2-26 CDRH3-27 55D1 CDRH1-21 CDRH2-26 CDRH3-27 48H3 CDRH1-21CDRH2-26 CDRH3-27 53C11 CDRH1-21 CDRH2-26 CDRH3-27 59G10.3 CDRH1-32CDRH2-40 CDRH3-45 51C10.1 CDRH1-13 CDRH2-13 CDRH3-13 59D10 v1 CDRH1-13CDRH2-13 CDRH3-13 59D10 v2 CDRH1-13 CDRH2-13 CDRH3-13 60F9 CDRH1-21CDRH2-41 CDRH3-47 48B4 CDRH1-21 CDRH2-41 CDRH3-47 52D6 CDRH1-21 CDRH2-41CDRH3-47 61G5 CDRH1-21 CDRH2-43 CDRH3-49 59G10.2 CDRH1-6 CDRH2-39CDRH3-44 51A8 CDRH1-12 CDRH2-12 CDRH3-12 53H5.2 CDRH1-12 CDRH2-23CDRH3-24 53F6 CDRH1-19 CDRH2-22 CDRH3-23 56C11 CDRH1-12 CDRH2-30CDRH3-33 49A10 CDRH1-6 CDRH2-6 CDRH3-6 48D4 CDRH1-6 CDRH2-6 CDRH3-6 49G2CDRH1-8 CDRH2-8 CDRH3-8 50C12 CDRH1-8 CDRH2-8 CDRH3-8 55G11 CDRH1-8CDRH2-8 CDRH3-8 52C1 CDRH1-12 CDRH2-19 CDRH3-19 55E9 CDRH1-23 CDRH2-28CDRH3-30 60D7 CDRH1-12 CDRH2-22 CDRH3-46 51C10.2 CDRH1-14 CDRH2-14CDRH3-14 55D3 CDRH1-22 CDRH2-27 CDRH3-28 57B12 CDRH1-28 CDRH2-34CDRH3-28 52C5 CDRH1-2 CDRH2-1 CDRH3-20 60G5.1 CDRH1-2 CDRH2-1 CDRH3-2055E4 CDRH1-2 CDRH2-1 CDRH3-20 49B11 CDRH1-2 CDRH2-1 CDRH3-20 50H10CDRH1-2 CDRH2-1 CDRH3-20 53C1 CDRH1-2 CDRH2-1 CDRH3-20 56G1 CDRH1-2CDRH2-1 CDRH3-20 48F3 CDRH1-2 CDRH2-2 CDRH3-2 48C9 CDRH1-1 CDRH2-1CDRH3-1 49A12 CDRH1-1 CDRH2-1 CDRH3-1 51E2 CDRH1-1 CDRH2-1 CDRH3-1 51E5CDRH1-2 CDRH2-15 CDRH3-15 53H5.3 CDRH1-20 CDRH2-24 CDRH3-25 56G3.3CDRH1-27 CDRH2-33 CDRH3-37 55B10 CDRH1-27 CDRH2-33 CDRH3-37 52B8CDRH1-16 CDRH2-18 CDRH3-18 55G5 CDRH1-24 CDRH2-29 CDRH3-31 52H2 CDRH1-18CDRH2-21 CDRH3-22 56G3.2 CDRH1-26 CDRH2-32 CDRH3-36 56E7 CDRH1-25CDRH2-31 CDRH3-34 57D9 CDRH1-29 CDRH2-35 CDRH3-39 48G4 CDRH1-5 CDRH2-5CDRH3-5 53C3.1 CDRH1-5 CDRH2-5 CDRH3-5 50G1 CDRH1-11 CDRH2-11 CDRH3-1158C2 CDRH1-6 CDRH2-36 CDRH3-40 63H11 CDRH1-35 CDRH2-34 CDRH3-51 61H5CDRH1-27 CDRH2-72 CDRH3-37 52B9 CDRH1-27 CDRH2-72 CDRH3-37 54H10.3CDRH1-43 CDRH2-74 CDRH3-81 50G5 v1 CDRH1-37 CDRH2-73 CDRH3-35 50G5 v2CDRH1-37 CDRH2-73 CDRH3-35 51C1 CDRH1-2 CDRH2-1 CDRH3-20 53C3.2 CDRH1-39CDRH2-77 CDRH3-43 50D4 CDRH1-41 CDRH2-75 CDRH3-80 55A7 CDRH1-24 CDRH2-18CDRH3-38 55E6 CDRH1-3 CDRH2-76 CDRH3-29 61E1 CDRH1-42 CDRH2-35 CDRH3-26

In an additional aspect, an antigen binding protein includes thefollowing associations of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3presented for convenience in tablular form and in reference to the clonesource of the association:

TABLE 6 CDRH and CDRL Associations Clone ID CDRL1 CDRL2 CDRL3 CDRH1CDRH2 CDRH3 63G8 CDRL1-13 CDRL2-29 CDRL3-41 CDRH1-34 CDRH2-12 CDRH3-5064A8 CDRL1-13 CDRL2-29 CDRL3-41 CDRH1-34 CDRH2-12 CDRH3-50 67B4 CDRL1-13CDRL2-29 CDRL3-41 CDRH1-34 CDRH2-12 CDRH3-50 68D3 CDRL1-13 CDRL2-29CDRL3-41 CDRH1-34 CDRH2-12 CDRH3-50 64E6 CDRL1-46 CDRL2-34 CDRL3-42CDRH1-35 CDRH2-44 CDRH3-51 65E8 CDRL1-46 CDRL2-34 CDRL3-42 CDRH1-35CDRH2-44 CDRH3-51 65F11 CDRL1-46 CDRL2-34 CDRL3-42 CDRH1-35 CDRH2-44CDRH3-51 67G7 CDRL1-46 CDRL2-34 CDRL3-42 CDRH1-35 CDRH2-44 CDRH3-51 63B6CDRL1-47 CDRL2-3 CDRL3-43 CDRH1-36 CDRH2-45 CDRH3-52 64D4 CDRL1-47CDRL2-3 CDRL3-43 CDRH1-36 CDRH2-45 CDRH3-52 65C3 CDRL1-48 CDRL2-36CDRL3-44 CDRH1-24 CDRH2-46 CDRH3-53 68D5 CDRL1-48 CDRL2-36 CDRL3-44CDRH1-24 CDRH2-46 CDRH3-53 63E6 CDRL1-49 CDRL2-14 CDRL3-45 CDRH1-37CDRH2-47 CDRH3-54 66F7 CDRL1-50 CDRL2-14 CDRL3-45 CDRH1-37 CDRH2-47CDRH3-54 64H5 CDRL1-51 CDRL2-37 CDRL3-46 CDRH1-12 CDRH2-48 CDRH3-55 65G4CDRL1-51 CDRL2-37 CDRL3-46 CDRH1-12 CDRH2-48 CDRH3-55 67G10v1 CDRL1-52CDRL2-38 CDRL3-47 CDRH1-38 CDRH2-49 CDRH3-56 67G10v2 CDRL1-53 CDRL2-39CDRL3-48 CDRH1-38 CDRH2-49 CDRH3-56 66B4 CDRL1-57 CDRL2-40 CDRL3-50CDRH1-15 CDRH2-53 CDRH3-59 66G2 CDRL1-22 CDRL2-41 CDRL3-51 CDRH1-12CDRH2-54 CDRH3-50 68G5 CDRL1-59 CDRL2-42 CDRL3-52 CDRH1-12 CDRH2-55CDRH3-60 63F5 CDRL1-54 CDRL2-20 CDRL3-42 CDRH1-35 CDRH2-50 CDRH3-51 66F6CDRL1-46 CDRL2-35 CDRL3-42 CDRH1-35 CDRH2-34 CDRH3-51 65C1 CDRL1-56CDRL2-35 CDRL3-42 CDRH1-35 CDRH2-52 CDRH3-58 64A7 CDRL1-55 CDRL2-20CDRL3-49 CDRH1-40 CDRH2-51 CDRH3-57 66D4 CDRL1-60 CDRL2-14 CDRL3-53CDRH1-43 CDRH2-56 CDRH3-61 65B1 CDRL1-61 CDRL2-43 CDRL3-15 CDRH1-44CDRH2-57 CDRH3-62 67A4 CDRL1-62 CDRL2-25 CDRL3-55 CDRH1-45 CDRH2-58CDRH3-63 65B4 CDRL1-63 CDRL2-25 CDRL3-55 CDRH1-46 CDRH2-59 CDRH3-6463A10 CDRL1-52 CDRL2-45 CDRL3-56 CDRH1-38 CDRH2-60 CDRH3-56 65H11CDRL1-65 CDRL2-38 CDRL3-57 CDRH1-38 CDRH2-61 CDRH3-56 64C8 CDRL1-66CDRL2-47 CDRL3-58 CDRH1-12 CDRH2-62 CDRH3-65 65E3 CDRL1-51 CDRL2-42CDRL3-59 CDRH1-47 CDRH2-63 CDRH3-66 65D4 CDRL1-67 CDRL2-42 CDRL3-60CDRH1-48 CDRH2-22 CDRH3-67 65D1 CDRL1-39 CDRL2-32 CDRL3-61 CDRH1-49CDRH2-64 CDRH3-68 67G8 CDRL1-69 CDRL2-37 CDRL3-59 CDRH1-12 CDRH2-65CDRH3-69 65B7 CDRL1-70 CDRL2-20 CDRL3-62 CDRH1-50 CDRH2-52 CDRH3-70 64A6CDRL1-71 CDRL2-48 CDRL3-63 CDRH1-14 CDRH2-66 CDRH3-71 65F9 CDRL1-72CDRL2-15 CDRL3-63 CDRH1-36 CDRH2-34 CDRH3-72 67F5 CDRL1-72 CDRL2-49CDRL3-64 CDRH1-24 CDRH2-67 CDRH3-53 64B10 CDRL1-73 CDRL2-50 CDRL3-17CDRH1-36 CDRH2-68 CDRH3-73 68C8 CDRL1-74 CDRL2-16 CDRL3-17 CDRH1-51CDRH2-69 CDRH3-74 67A5 CDRL1-75 CDRL2-5 CDRL3-66 CDRH1-25 CDRH2-31CDRH3-75 67C10 CDRL1-75 CDRL2-5 CDRL3-5 CDRH1-25 CDRH2-31 CDRH3-76 64H6CDRL1-51 CDRL2-37 CDRL3-68 CDRH1-25 CDRH2-70 CDRH3-77 63F9 CDRL1-76CDRL2-51 CDRL3-69 CDRH1-52 CDRH2-71 CDRH3-78 67F6 CDRL1-77 CDRL2-52CDRL3-5 CDRH1-53 CDRH2-31 CDRH3-79 48H11 CDRL1-4 CDRL2-4 CDRL3-4 CDRH1-4CDRH2-4 CDRH3-4 52A8 CDRL1-15 CDRL2-14 CDRL3-15 CDRH1-15 CDRH2-17CDRH3-17 52F8 CDRL1-19 CDRL2-17 CDRL3-19 CDRH1-17 CDRH2-20 CDRH3-2149H12 CDRL1-9 CDRL2-8 CDRL3-9 CDRH1-10 CDRH2-10 CDRH3-10 54A1 CDRL1-24CDRL2-6 CDRL3-9 CDRH1-10 CDRH2-25 CDRH3-10 55G9 CDRL1-24 CDRL2-6 CDRL3-9CDRH1-10 CDRH2-25 CDRH3-10 49C8 CDRL1-6 CDRL2-6 CDRL3-6 CDRH1-7 CDRH2-7CDRH3-7 52H1 CDRL1-6 CDRL2-6 CDRL3-6 CDRH1-7 CDRH2-7 CDRH3-7 60G5.2CDRL1-44 CDRL2-32 CDRL3-40 CDRH1-33 CDRH2-42 CDRH3-48 49G3 CDRL1-8CDRL2-7 CDRL3-8 CDRH1-9 CDRH2-9 CDRH3-9 59A10 CDRL1-14 CDRL2-28 CDRL3-14CDRH1-30 CDRH2-37 CDRH3-41 49H4 CDRL1-14 CDRL2-28 CDRL3-14 CDRH1-30CDRH2-37 CDRH3-41 48F8 CDRL1-3 CDRL2-3 CDRL3-3 CDRH1-3 CDRH2-3 CDRH3-353B9 CDRL1-3 CDRL2-3 CDRL3-3 CDRH1-3 CDRH2-3 CDRH3-3 56B4 CDRL1-3CDRL2-3 CDRL3-3 CDRH1-3 CDRH2-3 CDRH3-3 57E7 CDRL1-3 CDRL2-3 CDRL3-3CDRH1-3 CDRH2-3 CDRH3-3 57F11 CDRL1-3 CDRL2-3 CDRL3-3 CDRH1-3 CDRH2-3CDRH3-3 59C9 CDRL1-37 CDRL2-29 CDRL3-14 CDRH1-31 CDRH2-38 CDRH3-42 58A5CDRL1-37 CDRL2-29 CDRL3-14 CDRH1-31 CDRH2-38 CDRH3-42 57A4 CDRL1-37CDRL2-29 CDRL3-14 CDRH1-31 CDRH2-38 CDRH3-42 57F9 CDRL1-37 CDRL2-29CDRL3-14 CDRH1-31 CDRH2-38 CDRH3-42 51G2 CDRL1-14 CDRL2-13 CDRL3-14CDRH1-3 CDRH2-16 CDRH3-16 56A7 CDRL1-29 CDRL2-24 CDRL3-14 CDRH1-3CDRH2-16 CDRH3-32 56E4 CDRL1-29 CDRL2-24 CDRL3-14 CDRH1-3 CDRH2-16CDRH3-32 54H10.1 CDRL1-25 CDRL2-20 CDRL3-24 CDRH1-21 CDRH2-26 CDRH3-2755D1 CDRL1-25 CDRL2-20 CDRL3-24 CDRH1-21 CDRH2-26 CDRH3-27 48H3 CDRL1-25CDRL2-20 CDRL3-24 CDRH1-21 CDRH2-26 CDRH3-27 53C11 CDRL1-25 CDRL2-20CDRL3-24 CDRH1-21 CDRH2-26 CDRH3-27 59G10.3 CDRL1-41 CDRL2-16 CDRL3-37CDRH1-32 CDRH2-40 CDRH3-45 51C10.1 CDRL1-12 CDRL2-10 CDRL3-11 CDRH1-13CDRH2-13 CDRH3-13 59D10v1 CDRL1-38 CDRL2-10 CDRL3-34 CDRH1-13 CDRH2-13CDRH3-13 59D10v2 CDRL1-39 CDRL2-30 CDRL3-35 CDRH1-13 CDRH2-13 CDRH3-1360F9 CDRL1-43 CDRL2-31 CDRL3-39 CDRH1-21 CDRH2-41 CDRH3-47 48B4 CDRL1-43CDRL2-31 CDRL3-39 CDRH1-21 CDRH2-41 CDRH3-47 52D6 CDRL1-43 CDRL2-31CDRL3-39 CDRH1-21 CDRH2-41 CDRH3-47 61G5 CDRL1-45 CDRL2-33 CDRL3-39CDRH1-21 CDRH2-43 CDRH3-49 59G10.2 CDRL1-40 CDRL2-11 CDRL3-36 CDRH1-6CDRH2-39 CDRH3-44 51A8 CDRL1-10 CDRL2-9 CDRL3-10 CDRH1-12 CDRH2-12CDRH3-12 53H5.2 CDRL1-22 CDRL2-14 CDRL3-22 CDRH1-12 CDRH2-23 CDRH3-2453F6 CDRL1-21 CDRL2-19 CDRL3-21 CDRH1-19 CDRH2-22 CDRH3-23 56C11CDRL1-30 CDRL2-25 CDRL3-28 CDRH1-12 CDRH2-30 CDRH3-33 49A10 CDRL1-5CDRL2-5 CDRL3-5 CDRH1-6 CDRH2-6 CDRH3-6 48D4 CDRL1-5 CDRL2-5 CDRL3-5CDRH1-6 CDRH2-6 CDRH3-6 49G2 CDRL1-7 CDRL2-5 CDRL3-7 CDRH1-8 CDRH2-8CDRH3-8 50C12 CDRL1-7 CDRL2-5 CDRL3-7 CDRH1-8 CDRH2-8 CDRH3-8 55G11CDRL1-7 CDRL2-5 CDRL3-7 CDRH1-8 CDRH2-8 CDRH3-8 52C1 CDRL1-17 CDRL2-16CDRL3-17 CDRH1-12 CDRH2-19 CDRH3-19 55E9 CDRL1-27 CDRL2-17 CDRL3-26CDRH1-23 CDRH2-28 CDRH3-30 60D7 CDRL1-1 CDRL2-5 CDRL3-38 CDRH1-12CDRH2-22 CDRH3-46 51C10.2 CDRL1-12 CDRL2-11 CDRL3-12 CDRH1-14 CDRH2-14CDRH3-14 55D3 CDRL1-26 CDRL2-14 CDRL3-25 CDRH1-22 CDRH2-27 CDRH3-2857B12 CDRL1-34 CDRL2-14 CDRL3-32 CDRH1-28 CDRH2-34 CDRH3-28 52C5CDRL1-18 CDRL2-14 CDRL3-18 CDRH1-2 CDRH2-1 CDRH3-20 60G5.1 CDRL1-18CDRL2-14 CDRL3-18 CDRH1-2 CDRH2-1 CDRH3-20 55E4 CDRL1-18 CDRL2-21CDRL3-18 CDRH1-2 CDRH2-1 CDRH3-20 49B11 CDRL1-18 CDRL2-21 CDRL3-18CDRH1-2 CDRH2-1 CDRH3-20 50H10 CDRL1-18 CDRL2-21 CDRL3-18 CDRH1-2CDRH2-1 CDRH3-20 53C1 CDRL1-18 CDRL2-21 CDRL3-18 CDRH1-2 CDRH2-1CDRH3-20 56G1 CDRL1-18 CDRL2-14 CDRL3-30 CDRH1-2 CDRH2-1 CDRH3-20 48F3CDRL1-2 CDRL2-2 CDRL3-2 CDRH1-2 CDRH2-2 CDRH3-2 48C9 CDRL1-1 CDRL2-1CDRL3-1 CDRH1-1 CDRH2-1 CDRH3-1 49A12 CDRL1-1 CDRL2-1 CDRL3-1 CDRH1-1CDRH2-1 CDRH3-1 51E2 CDRL1-1 CDRL2-1 CDRL3-1 CDRH1-1 CDRH2-1 CDRH3-151E5 CDRL1-13 CDRL2-12 CDRL3-13 CDRH1-2 CDRH2-15 CDRH3-15 53H5.3CDRL1-23 CDRL2-15 CDRL3-23 CDRH1-20 CDRH2-24 CDRH3-25 56G3.3 CDRL1-33CDRL2-27 CDRL3-31 CDRH1-27 CDRH2-33 CDRH3-37 55B10 CDRL1-33 CDRL2-27CDRL3-31 CDRH1-27 CDRH2-33 CDRH3-37 52B8 CDRL1-16 CDRL2-15 CDRL3-16CDRH1-16 CDRH2-18 CDRH3-18 55G5 CDRL1-28 CDRL2-23 CDRL3-27 CDRH1-24CDRH2-29 CDRH3-31 52H2 CDRL1-20 CDRL2-18 CDRL3-20 CDRH1-18 CDRH2-21CDRH3-22 56G3.2 CDRL1-32 CDRL2-26 CDRL3-16 CDRH1-26 CDRH2-32 CDRH3-3656E7 CDRL1-31 CDRL2-7 CDRL3-29 CDRH1-25 CDRH2-31 CDRH3-34 57D9 CDRL1-35CDRL2-20 CDRL3-33 CDRH1-29 CDRH2-35 CDRH3-39 61H5 CDRL1-33 CDRL2-20CDRL3-31 CDRH1-27 CDRH2-72 CDRH3-37 52B9 CDRL1-33 CDRL2-20 CDRL3-31CDRH1-27 CDRH2-72 CDRH3-37 48G4 CDRL1-79 CDRL2-35 CDRL3-71 CDRH1-5CDRH2-5 CDRH3-5 53C3.1 CDRL1-79 CDRL2-35 CDRL3-71 CDRH1-5 CDRH2-5CDRH3-5 50G1 CDRL1-7 CDRL2-5 CDRL3-38 CDRH1-11 CDRH2-11 CDRH3-11 58C2CDRL1-81 CDRL2-5 CDRL3-66 CDRH1-6 CDRH2-36 CDRH3-40 54H10.3 CDRL1-42CDRL2-46 CDRL3-53 CDRH1-43 CDRH2-74 CDRH3-81 50G5v1 CDRL1-22 CDRL2-14CDRL3-72 CDRH1-37 CDRH2-73 CDRH3-35 50G5v2 CDRL1-78 CDRL2-22 CDRL3-75CDRH1-37 CDRH2-73 CDRH3-35 51C1 CDRL1-18 CDRL2-14 CDRL3-18 CDRH1-2CDRH2-1 CDRH3-20 53C3.2 CDRL1-36 CDRL2-44 CDRL3-70 CDRH1-39 CDRH2-77CDRH3-43 50D4 CDRL1-26 CDRL2-53 CDRL3-74 CDRH1-41 CDRH2-75 CDRH3-80 55A7CDRL1-58 CDRL2-14 CDRL3-54 CDRH1-24 CDRH2-18 CDRH3-38 55E6 CDRL1-64CDRL2-20 CDRL3-65 CDRH1-3 CDRH2-76 CDRH3-29 61E1 CDRL1-68 CDRL2-14CDRL3-67 CDRH1-42 CDRH2-35 CDRH3-26 63H11 CDRL1-46 CDRL2-34 CDRL3-42CDRH1-35 CDRH2-34 CDRH3-51

Consensus Sequences

In yet another aspect, the CDRs disclosed herein include consensussequences derived from groups of related monoclonal antibodies. Asdescribed herein, a “consensus sequence” refers to amino acid sequenceshaving conserved amino acids common among a number of sequences andvariable amino acids that vary within a given amino acid sequences. TheCDR consensus sequences provided include CDRs corresponding to each ofCDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3.

Consensus sequences were determined using standard analyses of the CDRscorresponding to the V_(H) and V_(L) of the disclosed antigen bindingproteins shown in Tables 3A and 3B, some of which specifically bind to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c. The consensus sequences can be determined by keepingthe CDRs contiguous within the same sequence corresponding to a V_(H) orV_(L).

Light Chain CDR3

Group 1 (SEQ ID NO: 1439) QQFGSSLT Group 2 (SEQ ID NO: 1440) QQS Y S T SLT (SEQ ID NO: 1441) QQS Y S S P LT (SEQ ID NO: 1442) QQS F S T P LT(SEQ ID NO: 1443) QQS X ₁ S X ₂ X ₃ LT wherein X₁ is Y or F; X₂ is T orS; and X₃ is P or S. Group 3 (SEQ ID NO: 1444) LQ R N SYP L T (SEQ IDNO: 1445) LQ H N SYP R T (SEQ ID NO: 1446) LQ H S SYP L T (SEQ ID NO:1447) LQ X ₄ X ₅ SYP X ₆ T wherein X₄ is H or R; X₅ is N or S; and X₆ isL or R. Group 4 (SEQ ID NO: 1448) MQR I EFP L T (SEQ ID NO: 1449) MQR IEFP I T (SEQ ID NO: 1450) MQR L EFP I T (SEQ ID NO: 1451) MQR X ₇ EFP X₈ T wherein X₇ is I or L; and X₈ us I or L. Group 5 (SEQ ID NO: 1452) QV WDS N P VV (SEQ ID NO: 1453) Q L WDS S T VV (SEQ ID NO: 1454) Q V WDSS S VV (SEQ ID NO: 1455) Q V WDS S P VV (SEQ ID NO: 1456) Q V WDS S T VV(SEQ ID NO: 1457) Q X ₉ WDS X ₁₀ X ₁₁ VV wherein X₉ is V or L; X₁₀ is Sor N; and X₁₁ is T, P or S. Group 6 (SEQ ID NO: 1458) QQYN N WP L T (SEQID NO: 1459) QQYN N WP W T (SEQ ID NO: 1460) QQYN T WP W T (SEQ ID NO:1461) QQYN X ₁₂ WP X ₁₃ T wherein X₁₂ is N or T; and X₁₃ is W or L.Group 7 (SEQ ID NO: 1462) QVWDSS S D H V V (SEQ ID NO: 1463) QVWDSS S DV V (SEQ ID NO: 1464) QVWDSS C D G V (SEQ ID NO: 1465) QVWDSS S D G V(SEQ ID NO: 1466) QVWDSS X ₁₄ D X ₁₅ V X ₁₆ wherein X₁₄ is S or C; X₁₅is H, V or G; and X₁₆ is V or absent. Group 8 (SEQ ID NO: 1467) QQSS SIPWT (SEQ ID NO: 1468) QQSS T IPWT (SEQ ID NO: 1469) QQSS X ₁₇ IPWTwherein X₁₇ is S or T. Group 9 (SEQ ID NO: 1470) QQTNSFPPWT Group 10(SEQ ID NO: 1471) GTWDSSLS A V V (SEQ ID NO: 1472) GTWDSSLS V V V (SEQID NO: 1473) GTWDSSLS A M V (SEQ ID NO: 1474) GTWDSSLS X ₁₈ X ₁₉ Vwherein X₁₈ is A or V; and X₁₉ is V or M. Group 11 (SEQ ID NO: 1475)QQYDNLP L T (SEQ ID NO: 1476) QQYDNLP F T (SEQ ID NO: 1477) QQYDNLP X ₂₀T wherein X₂₀ is L or F. Group 12 (SEQ ID NO: 1478) QQYGSS P PWT (SEQ IDNO: 1479) QQYGSS PWT (SEQ ID NO: 1480) QQYGSS X ₂₁ PWT wherein X₂₁ is Por absent. Group 13 (SEQ ID NO: 1481) QQYG R S L FT (SEQ ID NO: 1482)QQYG T S P FT (SEQ ID NO: 1483) QQYG X ₂₂ S X ₂₃ FT wherein X₂₂ is R orT; and X₂₃ is L or P. Group 14 (SEQ ID NO: 1484) QQYGSS R S (SEQ ID NO:1485) QQYGSS P R S (SEQ ID NO: 1486) QQYGSS R T (SEQ ID NO: 1487) QQYGSSC S (SEQ ID NO: 1488) QQYGSS X ₂₄ X ₂₅ X ₂₆ wherein X₂₄ is P or absent;X₂₅ is R or C and X₂₆ is S or T. Group 15 (SEQ ID NO: 1489) QADWSS T T WV (SEQ ID NO: 1490) QADWSS T A V (SEQ ID NO: 1491) QADWSS T W V (SEQ IDNO: 1492) QAWDSS X ₂₇ T X ₂₈ V wherein X₂₇ is T or absent; and X₂₈ is Wor A. Group 16 (SEQ ID NO: 1493) QADWS G TV V (SEQ ID NO: 1494) QADWS TTV V (SEQ ID NO: 1495) QAWDS A TV I (SEQ ID NO: 1496) QAWDS X ₂₉ TV X ₃₀wherein X₂₉ is G, T, A or absent; and X₃₀ is V or I. Group 17 (SEQ IDNO: 1497) QQ S YSA T FT (SEQ ID NO: 1498) QQ T YSA P FT (SEQ ID NO:1499) QQ X ₃₁ YSA X ₃₂ FT wherein X₃₁ is S or T; and X₃₂ is T or P.Group 18 (SEQ ID NO: 1500) QQYN I YPRT (SEQ ID NO: 1501) QQYN T YPRT(SEQ ID NO: 1502) QQYN X ₃₃ YPRT wherein X₃₃ is I or T. Group 19 (SEQ IDNO: 1503) HQ S S DLPLT (SEQ ID NO: 1504) HQ Y D DLPLT (SEQ ID NO: 1505)HQ X ₃₄ X ₃₅ DLPLT wherein X₃₄ is S or Y; and X₃₅ is S or D. Group 20(SEQ ID NO: 1506) MQALQT P F T (SEQ ID NO: 1507) MQALQT L I T (SEQ IDNO: 1508) MQALQT X ₃₆ X ₃₇ T wherein X₃₆ is P or L; and X₃₇ is F or I.Group 21 (SEQ ID NO: 1509) QQFGRSFT Group 22 (SEQ ID NO: 1510) YSTDSS VNHVV (SEQ ID NO: 1511) YSTDSS G NHVV (SEQ ID NO: 1512) YSTDSS X ₃₈ NHVVwherein X₃₈ is V or G.

Light Chain CDR2

Group 1 (SEQ ID NO: 1513) A ASSL Q S (SEQ ID NO: 1514) S ASSL Q S (SEQID NO: 1515) A ASSL Q F (SEQ ID NO: 1516) A ASSL K S (SEQ ID NO: 1517) X₃₉ ASSL X ₄₀ X ₄₁ wherein X₃₉ is A or S; X₄₀ is Q or K; and X₄₁ is S orF. Group 2 (SEQ ID NO: 1518) G A S S R A T (SEQ ID NO: 1519) G A S S R DT (SEQ ID NO: 1520) G T S T R A T (SEQ ID NO: 1521) G A S T R A T (SEQID NO: 1522) G A S A R A T (SEQ ID NO: 1523) G A S R R A T (SEQ ID NO:1524) G A S N R A T (SEQ ID NO: 1525) G X ₄₂ S X ₄₃ R X ₄₄ T wherein X₄₂is A or T; X₄₃ is S, T, A, R or N; and X₄₄ is A or D. Group 3 (SEQ IDNO: 1526) GAFSRA S (SEQ ID NO: 1527) GAFSRA T (SEQ ID NO: 1528) GAFSRA X₄₅ wherein X₄₅ is S or T. Group 4 (SEQ ID NO: 1529) Q D T KRPS (SEQ IDNO: 1530) R D S KRPS (SEQ ID NO: 1531) E D S KRPS (SEQ ID NO: 1532) Q DS KRPS (SEQ ID NO: 1533) X ₄₆ D X ₄₇ KRPS wherein X₄₆ is Q, R or E; andX₄₇ is T or S. Group 5 (SEQ ID NO: 1534) TLS Y RAS (SEQ ID NO: 1535) TLSF RAS (SEQ ID NO: 1536) TLS X ₄₈ RAS wherein X₄₈ is Y or F. Group 6 (SEQID NO: 1537) AASNLQ R (SEQ ID NO: 1538) AASNLQ S (SEQ ID NO: 1539)AASNLQ X ₄₉ wherein X49 is R or S. Group 7 (SEQ ID NO: 1540) G A SNRA I(SEQ ID NO: 1541) G S SNRA I (SEQ ID NO: 1542) G S SNRA T (SEQ ID NO:1543) G X ₅₀ SNRA X ₅₁ wherein X₅₀ is A or S; and X₅₁ is I or T. Group 8(SEQ ID NO: 1544) D A S S LQS (SEQ ID NO: 1545) D A S T LQS (SEQ ID NO:1546) G A S S LQS (SEQ ID NO: 1547) G A S N LQS (SEQ ID NO: 1548) X ₅₂ AS X ₅₃ LQS wherein X₅₂ is D or G; and X₅₃ is S, T or N. Group 9 (SEQ IDNO: 1549) DN N KRPS (SEQ ID NO: 1550) DN D KRPS (SEQ ID NO: 1551) DN X₅₃ KRPS wherein X₅₃ is N or D. Group 10 (SEQ ID NO: 1552) D A SNLET (SEQID NO: 1553) D V SNLET (SEQ ID NO: 1554) D X ₅₄ SNLET wherein X₅₄ is Aor V. Group 11 (SEQ ID NO: 1555) L G SNRAS (SEQ ID NO: 1556) L D SNRAS(SEQ ID NO: 1557) L X ₅₅ SNRAS wherein X₅₅ is G or D. Group 12 (SEQ IDNO: 1558) Q D N K RPS (SEQ ID NO: 1559) Q N N K RPS (SEQ ID NO: 1560) QD N E RPS (SEQ ID NO: 1561) Q X ₅₆ N X ₅₇ RPS wherein X₅₆ is D or N; andX₅₇ is K or E. Group 13 (SEQ ID NO: 1562) RDRNRPS Group 14 (SEQ ID NO:1563) S DSNRPS (SEQ ID NO: 1564) C DSNRPS (SEQ ID NO: 1565) X ₅₈ DSNRPSwherein X₅₈ is S or C. Group 15 (SEQ ID NO: 1566) DDSDRPS Group 16 (SEQID NO: 1567) A V SSLQS (SEQ ID NO: 1568) A S SSLQS (SEQ ID NO: 1569) A X₅₉ SSLQS wherein X₅₉ is S or V. Group 17 (SEQ ID NO: 1570) T A SSLQS(SEQ ID NO: 1571) T T SSLQS (SEQ ID NO: 1572) T X ₆₀ SSLQS wherein X₆₀is A or T. Group 18 (SEQ ID NO: 1573) K V SNWDS (SEQ ID NO: 1574) K GSNWDS (SEQ ID NO: 1575) K X ₆₁ SNWDS wherein X₆₁ is V or G.

Light Chain CDR1

Group 1 (SEQ ID NO: 1576) RAS Q S V S D I L A (SEQ ID NO: 1577) RAS P SV S S S Y L A (SEQ ID NO: 1578) RAS Q S F S S S Y L A (SEQ ID NO: 1579)RAS Q S V S R S H L A (SEQ ID NO: 1580) RAS Q S V S R D Y L A (SEQ IDNO: 1581) RAS Q S V S R N Y L A (SEQ ID NO: 1582) RAS Q S V S S M Y L A(SEQ ID NO: 1583) RAS Q S V S S Q L A (SEQ ID NO: 1584) RAS Q S I S S NL A (SEQ ID NO: 1585) RAS Q S V S S N L A (SEQ ID NO: 1586) RAS Q S V SS N V A (SEQ ID NO: 1587) RAS Q S V N S N L A (SEQ ID NO: 1588) RAS Q SV R S S S L A (SEQ ID NO: 1589) RAS Q S V S N S S L A (SEQ ID NO: 1590)RAS Q S V R N S S L A (SEQ ID NO: 1591) RAS X ₆₂ S X ₆₃ X ₆₄ X ₆₅ X ₆₆ X₆₇ X ₆₈ A wherein X₆₂ is P or Q; X₆₃ is V, I or F; X₆₄ is S, R orabsent; X₆₅ is S, R or N; X₆₆ is D, S, N or M; X₆₇ is I, Y, H, Q, N orS; and X₆₈ is L or V. Group 2 (SEQ ID NO: 1592) R A SQ I I S R YLN (SEQID NO: 1593) R T SQ S I S S YLN (SEQ ID NO: 1594) R A SQ S I S N YLN(SEQ ID NO: 1595) R T SQ S I S S YLN (SEQ ID NO: 1596) R A SQ T I S IYLN (SEQ ID NO: 1597) R A SQ R I S S YLN (SEQ ID NO: 1598) R A SQ S I SS YLN (SEQ ID NO: 1599) R A SQ N I R T YLN (SEQ ID NO: 1600) R A SQ N IR S YLN (SEQ ID NO: 1601) R A SQ N I N N YLN (SEQ ID NO: 1602) R X ₆₉ SQX ₇₀ I X ₇₁ X ₇₂ YLN wherein X₆₉ is A or T; X₇₀ is I, S, T or N; X₇₁ isR, S or N; and X₇₂ is R, S, N, or I. Group 3 (SEQ ID NO: 1603) GGN N IGSY N V H (SEQ ID NO: 1604) GGN N IGS I N V H (SEQ ID NO: 1605) GGN N IGSK S V Q (SEQ ID NO: 1606) GGN D IGS K S V H (SEQ ID NO: 1607) GGN N IGSK S V H (SEQ ID NO: 1608) GGN N IGS K T V H (SEQ ID NO: 1609) GGN N IGSK A V H (SEQ ID NO: 1610) GGN N IGS K N V H (SEQ ID NO: 1611) GGN D IGSK N V H (SEQ ID NO: 1612) GGN X ₇₃ IGS X ₇₄ X ₇₅ V X ₇₆ wherein X₇₃ isN, or D; X₇₄ is Y, I or K; X₇₅ is N, S, T or A; and X₇₆ is H or Q. Group4 (SEQ ID NO: 1613) RASQ D IRNDL G (SEQ ID NO: 1614) RASQ D IRNDL A (SEQID NO: 1615) RASQ G IRNDL G (SEQ ID NO: 1616) RASQ X ₇₇ IRNDL X ₇₈wherein X₇₇ is D or G; and X₇₈ is G or A. Group 5 (SEQ ID NO: 1617)RSSQSL L N S D A G T TYLD (SEQ ID NO: 1618) RSSQSL F D N D D G D TYLD(SEQ ID NO: 1619) RSSQSL L N S D D G N TYLD (SEQ ID NO: 1620) RSSQSL L DS D D G D TYLD (SEQ ID NO: 1621) RSSQSL L D S D D G N TYLD (SEQ ID NO:1622) RSSQSL X ₇₉ X ₈₀ X ₈₁ D X ₈₂ G X ₈₃ TYLD wherein X₇₉ is L or F;X₈₀ is N or D; X₈₁ is S or N; X₈₂ is A or D; and X₈₃ is T, D or N. Group6 (SEQ ID NO: 1623) SG N K LGDKY V C (SEQ ID NO: 1624) SG D K LGDKY V C(SEQ ID NO: 1625) SG D K LGDKY A C (SEQ ID NO: 1626) SG D E LGDKY A C(SEQ ID NO: 1627) SG D N LGDKY A F (SEQ ID NO: 1628) SG D N LGDKY A C(SEQ ID NO: 1629) SG X ₈₄ X ₈₅ LGDKY X ₈₆ X ₈₇ wherein X₈₄ is N or D;X₈₅ is K, E or N; X₈₆ is V or A; and X₈₇ is C or F. Group 7 (SEQ ID NO:1630) QASQ G I S N Y LN (SEQ ID NO: 1631) QASQ D I K K F LN (SEQ ID NO:1632) QASQ D I N I Y LN (SEQ ID NO: 1633) QASQ D I S I Y LN (SEQ ID NO:1634) QASQ D I T K Y LN (SEQ ID NO: 1635) QASQ X ₈₈ I X ₈₉ X ₉₀ X ₉₁ LNwherein X₈₈ is G or D; X₈₉ is S, K N or T; X₉₀ is N, K or I; and X₉₁ isY or F. Group 8 (SEQ ID NO: 1636) RASQ D I D S WL V (SEQ ID NO: 1637)RASQ G I S R WL A (SEQ ID NO: 1638) RASQ D I S S WL A (SEQ ID NO: 1639)RASQ G I S S WL A (SEQ ID NO: 1640) RASQ X ₉₂ I X ₉₃ X ₉₄ WL X ₉₅wherein X₉₂ is D or G; X₉₃ is D or S; X₉₄ is R or S; and X₉₅ is V or A.Group 9 (SEQ ID NO: 1641) SGSSSNIG N NYV A (SEQ ID NO: 1642) SGSSSNIG INYV S (SEQ ID NO: 1643) SGSSSNIG D NYV S (SEQ ID NO: 1644) SGSSSNIG NNYV S (SEQ ID NO: 1645) SGSSSNIG X ₉₆ NYV X ₉₇ wherein X₉₆ is N, I or D;and X₉₇ is A or S. Group 10 (SEQ ID NO: 1646) RAS Q DISNYLA (SEQ ID NO:1647) RAS H DISNYLA (SEQ ID NO: 1648) RAS X ₉₈ DISNYLA wherein X₉₈ is Qor H. Group 11 (SEQ ID NO: 1649) RASQ R V P SSY I V (SEQ ID NO: 1650)RASQ R V P SSY L V (SEQ ID NO: 1651) RASQ S V A SSY L V (SEQ ID NO:1652) RASQ X ₉₉ V X ₁₀₀ SSY X ₁₀₁ V wherein X₉₉ is R or S; X₁₀₀ is P orA; and X₁₀₁ is I or L. Group 12 (SEQ ID NO: 1653) RSSQSL L HSNG Y NYLD(SEQ ID NO: 1654) RSSQSL L HSNG F NYLD (SEQ ID NO: 1655) RSSQSL Q HSNG YNYLD (SEQ ID NO: 1656) RSSQSL X ₁₀₂ HSNG X ₁₀₃ NYLD wherein X₁₀₂ is L orQ; and X₁₀₃ is Y or F. Group 13 (SEQ ID NO: 1657) RASQT V RN N YLA (SEQID NO: 1658) RASQT I RN S YLA (SEQ ID NO: 1659) RASQT X ₁₀₄ RN X ₁₀₅ YLAwherein X₁₀₄ is V or I; and X₁₀₅ is N or S. Group 14 (SEQ ID NO: 1660)RSS Q R LVYSDGNTYLN (SEQ ID NO: 1661) RSS P S LVYSDGNTYLN (SEQ ID NO:1662) RSS X ₁₀₆ X ₁₀₇ LVYSDGNTYLN wherein X₁₀₆ is Q or P; and X₁₀₇ is Ror S. Group 15 (SEQ ID NO: 1663) SGDA L PKKYA Y (SEQ ID NO: 1664) SGDA VPKKYA N (SEQ ID NO: 1665) SGDA X ₁₀₈ PKKYA X ₁₀₉ wherein X₁₀₈ is L or V;and X₁₀₉ is Y or N.

Heavy Chain CDR3

Group 1 (SEQ ID NO: 1666) MT T PYWYF D L (SEQ ID NO: 1667) MT S PYWYF DL (SEQ ID NO: 1668) MT T PYWYF G L (SEQ ID NO: 1669) MT X ₁₁₀ PYWYF X₁₁₁ L wherein X₁₁₀ is T or S; and X₁₁₁ is D or G. Group 2 (SEQ ID NO:1670) D R Y Y DFW S GYP Y F R YYG L DV (SEQ ID NO: 1671) D Q Y F DFW SGYP F F Y YYG M DV (SEQ ID NO: 1672) D Q D Y DFW S GYP Y F Y YYG M DV(SEQ ID NO: 1673) D Q N Y DFW N GYP Y Y F YYG M DV (SEQ ID NO: 1674) D QY Y DFW S GYP Y Y H YYG M DV (SEQ ID NO: 1675) D X ₁₁₂ X ₁₁₃ X ₁₁₄ DFW X₁₁₅ GYP X ₁₁₆ X ₁₁₇ X ₁₁₈ YYG X ₁₁₉ DV wherein X₁₁₂ is R or Q; X₁₁₃ isY, D or N; X₁₁₄ is Y or F; X₁₁₅ is S or N; X₁₁₆ is Y or F; X₁₁₇ is F orY; X₁₁₈ is R, Y, F or H; and X₁₁₉ is L or M. Group 3 (SEQ ID NO: 1676)VTGTDAFDF Group 4 (SEQ ID NO: 1677) TVTKEDYYYYGMDV Group 5 (SEQ ID NO:1678) DSSGSYYVEDYFDY Group 6 (SEQ ID NO: 1679) D W S IAVAG T FDY (SEQ IDNO: 1680) D L R IAVAG S FDY (SEQ ID NO: 1681) D X ₁₁₉ X ₁₂₀ IAVAG X ₁₂₁FDY wherein X₁₁₉ is W or L; X₁₂₀ is S or R; and X₁₂₁ is T or S. Group 7(SEQ ID NO: 1682) EYYYGSGSYYP Group 8 (SEQ ID NO: 1683) ELGDYPFFDY Group9 (SEQ ID NO: 1684) EYVAEAGFDY Group 10 (SEQ ID NO: 1685) VAAVYWYFDLGroup 11 (SEQ ID NO: 1686) YNWNYGAFDF Group 12 (SEQ ID NO: 1687) RASRGYRF GLAFAI (SEQ ID NO: 1688) RASRGYR Y GLAFAI (SEQ ID NO: 1689) RASRGYR X₁₂₂ GLAFAI wherein X₁₂₂ is F or Y. Group 13 (SEQ ID NO: 1690)DGITMVRGVTHYYGMDV Group 14 (SEQ ID NO: 1691) DH S SGWYYYGMDV (SEQ ID NO:1692) DH T SCWYYYGMDV (SEQ ID NO: 1693) DH X ₁₂₃ SCWYYYGMDV wherein X₁₂₃is S or T. Group 15 (SEQ ID NO: 1694) Y S T WDYYYG V DV (SEQ ID NO:1695) Y R D WDYYYG M DV (SEQ ID NO: 1696) Y X ₁₂₄ X ₁₂₅ WDYYYG X ₁₂₆ DVwherein X₁₂₄ is S or R; X₁₂₅ is T or D; and X₁₂₆ is V or M. Group 16(SEQ ID NO: 1697) VLHY S DS R GYSYY S D F (SEQ ID NO: 1698) VLHY Y DS SGYSYY F D Y (SEQ ID NO: 1699) VLHY X ₁₂₇ DS X ₁₂₈ GYSYY X ₁₂₉ D X ₁₃₀wherein X₁₂₇ is S or Y; X₁₂₈ is R or S; X₁₂₉ is S or F; and X₁₃₀ is F orY.

Heavy Chain CDR2

Group 1 (SEQ ID NO: 1700) N I Y Y S G T T Y F NPSLKS (SEQ ID NO: 1701) FI Y Y S G G T N Y NPSLKS (SEQ ID NO: 1702) Y I Y Y S G G T H Y NPSLKS(SEQ ID NO: 1703) Y I Y H S G S A Y Y NPSLKS (SEQ ID NO: 1704) Y I Y D SG S T Y Y NPSLKS (SEQ ID NO: 1705) S I Y Y S G T T Y Y NPSLKS (SEQ IDNO: 1706) M I Y Y S G T T Y Y NPSLKS (SEQ ID NO: 1707) Y I Y Y S G T T YY NPSLKS (SEQ ID NO: 1708) Y I Y Y S G S A Y Y NPSLKS (SEQ ID NO: 1709)Y I F Y S G S T Y Y NPSLKS (SEQ ID NO: 1710) Y L Y Y S G S T Y Y NPSLKS(SEQ ID NO: 1711) Y I Y Y S G S T Y Y NPSLKS (SEQ ID NO: 1712) Y I Y Y TG S T Y Y NPSLKS (SEQ ID NO: 1713) Y I Y Y T G S T N Y NPSLKS (SEQ IDNO: 1714) Y I Y Y S G N T N Y NPSLKS (SEQ ID NO: 1715) Y I Y Y S G S T NY NPSLKS (SEQ ID NO: 1716) X ₁₃₁ X ₁₃₂ X ₁₃₃ X ₁₃₄ X ₁₃₅ G X ₁₃₆ X ₁₃₇ X₁₃₈ X ₁₃₉ NPSLKS wherein X₁₃₁ is N, F, Y, S or M; X₁₃₂ is I or L; X₁₃₃is Y or F; X₁₃₄ is Y, H or D; X₁₃₅ is S or T; X₁₃₆ is T, G, S or T; X₁₃₇is T or A; X₁₃₈ is Y, N or H; and X₁₃₉ is F or Y. Group 2 (SEQ ID NO:1717) L I W Y DG D N K Y Y ADSVKG (SEQ ID NO: 1718) G I S Y DG S N K N YADSVKG (SEQ ID NO: 1719) I I W Y DG S N K N Y ADSVKG (SEQ ID NO: 1720) LI W Y DG S N K N Y ADSVKG (SEQ ID NO: 1721) L I W Y DG S N K D Y ADSVKG(SEQ ID NO: 1722) V I W Y DG S N K D Y ADSVKG (SEQ ID NO: 1723) L I S YDG S N K Y Y ADSVKG (SEQ ID NO: 1724) V I S Y DG S N K H Y ADSVKG (SEQID NO: 1725) V I S Y DG S N K Y Y ADSVKG (SEQ ID NO: 1726) V I W D DG SN K Y Y ADSVKG (SEQ ID NO: 1727) V I W D DG S N N Y Y ADSVKG (SEQ ID NO:1728) V I W Y DG S N K Y H ADSVKG (SEQ ID NO: 1729) V I W Y DG S N K Y YADSVKG (SEQ ID NO: 1730) V I W N DG N N K Y Y ADSVKG (SEQ ID NO: 1731) VI W N DG S N K N Y ADSVKG (SEQ ID NO: 1732) X ₁₄₀ I X ₁₄₁ X ₁₄₂ DG X ₁₄₃N X ₁₄₄ X ₁₄₅ X ₁₄₆ ADSVKG wherein X₁₄₀ is L, G, I or V; X₁₄₁ is W or S;X₁₄₂ is Y, D or N; X₁₄₃ is S or D; X₁₄₄ is K or N; X₁₄₅ is Y, N, D, orH; and X₁₄₆ is Y or H. Group 3 (SEQ ID NO: 1733) W I NP P SG A T N YAQKFR G (SEQ ID NO: 1734) W I NP N SG G T N YAQKF R G (SEQ ID NO: 1735) W INP N SG A T N YAQKF H G (SEQ ID NO: 1736) W I NP S SG D T K YAQKF Q G(SEQ ID NO: 1737) W M NP N SG A T K YAQKF Q G (SEQ ID NO: 1738) W I NP NSG A T K YAQKF Q G (SEQ ID NO: 1739) W I NP D SG G T N YAQKF Q G (SEQ IDNO: 1740) W I NP N SG G T D YAQKF Q G (SEQ ID NO: 1741) W X ₁₄₇ NP X ₁₄₈SG X ₁₄₉ T X ₁₅₀ YAQKF X ₁₅₁ G wherein X₁₄₇ is I or M; X₁₄₈ is P, N, Sor D; X₁₄₉ is A, G or D; X₁₅₀ is N, K, or D; X₁₅₁ is R, H or Q. Group 4(SEQ ID NO: 1742) EINHS E N TNYNPSLKS (SEQ ID NO: 1743) EINHS G TTNYNPSLKS (SEQ ID NO: 1744) EINHS X ₁₅₂ X ₁₅₃ TNYNPSLKS wherein X₁₅₂ isE or G; and X₁₅₃ is N or T. Group 5 (SEQ ID NO: 1745) IIYPGDS DTRYSPSFQG (SEQ ID NO: 1746) IIYPGDS E TRYSPSFQG (SEQ ID NO: 1747)IIYPGDS X ₁₅₄ TRYSPSFQG wherein X₁₅₄ is D or E. Group 6 (SEQ ID NO:1748) SISSSS T Y I YY A DS V KG (SEQ ID NO: 1749) SISSSS T Y I YY A DS LKG (SEQ ID NO: 1750) SISSSS S Y E YY V DS V KG (SEQ ID NO: 1751) SISSSSX ₁₅₅ Y X ₁₅₆ YY X ₁₅₇ DS X ₁₅₈ KG wherein X₁₅₅ is T or S; X₁₅₆ is I orE; X₁₅₇ is A or V; and X₁₅₈ is V or L. Group 7 (SEQ ID NO: 1752) RI K SKTDGGTT D YAAPVKG (SEQ ID NO: 1753) RI K S KTDGGTT E YAAPVKG (SEQ ID NO:1754) RI I G KTDGGTT D YAAPVKG (SEQ ID NO: 1755) RI X ₁₅₉ X ₁₆₀ KTDGGTTX ₁₆₁ YAAPVKG wherein X₁₅₉ is K or I; X₁₆₀ is S or G; and X₁₆₁ is D orE. Group 8 (SEQ ID NO: 1756) GISGSSAGTYYADSVGK Group 9 (SEQ ID NO: 1757)VIS D SGG S TYYADSVKG (SEQ ID NO: 1758) VIS G SGG D TYYADSVKG (SEQ IDNO: 1759) VIS X ₁₆₂ SGG X ₁₆₃ TYYADSVKG wherein X₁₆₂ is D or G; and X₁₆₃is S or D. Group 10 (SEQ ID NO: 1760) RTYYRSKWYNDYAVSVKS Group 11 (SEQID NO: 1761) RIY I SGSTNYNPSL E N (SEQ ID NO: 1762) RIY T SGSTNYNPSL K S(SEQ ID NO: 1763) RIY X ₁₆₄ SGSTNYNPSL X ₁₆₅ X ₁₆₆ wherein X₁₆₄ is I orT; X₁₆₅ is E or K; and X₁₆₆ is N or S. Group 12 (SEQ ID NO: 1764)WMNPYSGSTG Y AQ N FQ G (SEQ ID NO: 1765) WMNPYSGSTG L AQ R FQ D (SEQ IDNO: 1766) WMNPYSGSTG X ₁₆₇ AQ X ₁₆₈ FQ X ₁₆₉ wherein X₁₆₇ is Y or L;X₁₆₈ is N or R; and X₁₆₉ is G or D.

Heavy Chain CDR1

Group 1 (SEQ ID NO: 1767) SG V Y YW N (SEQ ID NO: 1768) SG V Y YW S (SEQID NO: 1769) SG G Y YW N (SEQ ID NO: 1770) SG G Y YW S (SEQ ID NO: 1771)SG D N TW S (SEQ ID NO: 1772) SG N Y TW S (SEQ ID NO: 1773) SG D Y TW T(SEQ ID NO: 1774) SG D Y TW S (SEQ ID NO: 1775) SG X ₁₇₀ X ₁₇₁ TW X ₁₇₂wherein X₁₇₀ is V, G, N or D; X₁₇₁ is Y or N; and X₁₇₂ is N, S or T.Group 2 (SEQ ID NO: 1776) T YYW S (SEQ ID NO: 1777) Y YYW S (SEQ ID NO:1778) S YYW S (SEQ ID NO: 1779) G YYW S (SEQ ID NO: 1780) G YYW T (SEQID NO: 1781) X ₁₇₃ YYW X ₁₇₄ wherein X₁₇₃ is T, S or G; and X₁₇₄ is S orT. Group 3 (SEQ ID NO: 1782) S Y GMH (SEQ ID NO: 1783) S F GMH (SEQ IDNO: 1784) T Y GMH (SEQ ID NO: 1785) F Y GMH (SEQ ID NO: 1786) X ₁₇₅ X₁₇₆ GMH wherein X₁₇₅ is S, T or F; and X₁₇₆ is Y or F. Group 4 (SEQ IDNO: 1787) SY A M S (SEQ ID NO: 1788) SY S M N (SEQ ID NO: 1789) SY S M S(SEQ ID NO: 1790) SY X ₁₇₇ M X ₁₇₈ wherein X₁₇₇ is A or S; and X₁₇₈ isS, N or M. Group 5 (SEQ ID NO: 1791) Y YY I H (SEQ ID NO: 1792) G YY L H(SEQ ID NO: 1793) G YY K H (SEQ ID NO: 1794) G YY T H (SEQ ID NO: 1795)G YY I H (SEQ ID NO: 1796) X ₁₇₉ YY X _(180 H) wherein X₁₇₉ is Y or G;and X₁₈₀ is I, L, K or T. Group 6 (SEQ ID NO: 1797) SYG I H (SEQ ID NO:1798) SYG L H (SEQ ID NO: 1799) SYG X ₁₈₁ H wherein X₁₈₁ is L or I.Group 7 (SEQ ID NO: 1800) NY G M H (SEQ ID NO: 1801) NY G M R (SEQ IDNO: 1802) NY N M H (SEQ ID NO: 1803) NY X ₁₈₂ M X ₁₈₃ wherein X₁₈₂ is Gor N; and X₁₈₃ is H, R or M. Group 8 (SEQ ID NO: 1804) S YWIG (SEQ IDNO: 1805) G YWIG (SEQ ID NO: 1806) X ₁₈₄ YWIG wherein X₁₈₄ is S or G.Group 9 (SEQ ID NO: 1807) GY Y MH (SEQ ID NO: 1808) GY F MH (SEQ ID NO:1809) GY X ₁₈₅ MH wherein X₁₈₅ is Y or F. Group 10 (SEQ ID NO: 1810) S YDI N (SEQ ID NO: 1811) S H DI N (SEQ ID NO: 1812) S Y DI D (SEQ ID NO:1813) S X ₁₈₆ DI X ₁₈₇ wherein X₁₈₆ is Y or H; and X₁₈₇ is N or D. Group11 (SEQ ID NO: 1814) N YAMS (SEQ ID NO: 1815) H YAMS (SEQ ID NO: 1816) X₁₈₈ YAMS wherein X₁₈₈ is N or H. Group 12 (SEQ ID NO: 1817) NAWMS Group13 (SEQ ID NO: 1818) SSSYYWG Group 14 (SEQ ID NO: 1819) D YYWN (SEQ IDNO: 1820) S YYWN (SEQ ID NO: 1821) X ₁₈₉ YYWN wherein X₁₈₉ is D or S.Group 15 (SEQ ID NO: 1822) SNSA T WN (SEQ ID NO: 1823) SNSA A WN (SEQ IDNO: 1824) SNSA X ₁₉₀ WN wherein X₁₉₀ is T or A. Group 16 (SEQ ID NO:1825) S YDMH (SEQ ID NO: 1826) T YDMH (SEQ ID NO: 1827) X ₁₉₁ YDMHwherein X₁₉₁ is S or T.

In some cases an antigen binding protein comprises at least one heavychain CDR1, CDR2, or CDR3 having one of the above consensus sequences.In some cases, an antigen binding protein comprises at least one lightchain CDR1, CDR2, or CDR3 having one of the above consensus sequences.In other cases, the antigen binding protein comprises at least two heavychain CDRs according to the determined consensus sequences, and/or atleast two light chain CDRs according to the determined consensussequences. In still other cases, the antigen binding protein comprisesat least three heavy chain CDRs according to the determined consensussequences, and/or at least three light chain CDRs according to thedetermined consensus sequences.

Exemplary Antigen Binding Proteins

According to one aspect, an isolated antigen binding protein comprising(a) one or more heavy chain complementary determining regions (CDRHs)comprising one or more of: (i) a CDRH1 selected from the groupconsisting of SEQ ID NOS 603-655; (ii) a CDRH2 selected from the groupconsisting of SEQ ID NOS 656-732; (iii) a CDRH3 selected from the groupconsisting of SEQ ID NOS 733-813; and (iv) a CDRH of (i), (ii) and (iii)that comprises ten, nine, eight, seven, six, five, four, three, two orone amino acid substitutions, deletions, insertions and combinationsthereof; (b) one or more light chain complementary determining regions(CDRLs) comprising one or more of: (i) a CDRL1 selected from the groupconsisting of SEQ ID NOS 814-893; (ii) a CDRL2 comprising one or more ofSEQ ID NOS 894-946; (iii) a CDRL3 comprising one or more of SEQ ID NOS947-1020; and (iv) a CDRL of (i), (ii) and (iii) that comprises ten,nine, eight, seven, six, five, four, three, four, two or one amino acidsubstitutions, deletions or insertions and combinations thereof; or (c)one or more heavy chain CDRHs of (a) and one or more light chain CDRLsof (b).

In another embodiment, the CDRHs have at least 70%, 75%, 80%, 85%, 90%,95%, 96%, 97%, 98% or 99% sequence identity with an amino acid sequenceselected from the group consisting of SEQ ID NOS 603-813, and/or theCDRLs have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%sequence identity with an amino acid sequence selected from the groupconsisting of SEQ ID NOS 814-1020. In a further embodiment, the VH isselected from the group consisting of SEQ ID NOS 316-409, and/or theV_(L) is selected from the group consisting of SEQ ID NOS 217-315.

According to one aspect, an isolated antigen binding protein comprising(a) one or more variable heavy chains (V_(H)s) comprising one or moreof: (i) SEQ ID NOS 316-409; and (ii) a V_(H) of (i) that comprises ten,nine, eight, seven, six, five, four, three, two or one amino acidsubstitutions, deletions, insertions and combinations thereof; (b) oneor more variable light chains (V_(L)s) selected from the groupconsisting of: (i) SEQ ID NOS 217-315, and (ii) a V_(L) of (i) thatcomprises ten, nine, eight, seven, six, five, four, three, two or oneamino acid substitutions, deletions, insertions and combinationsthereof; or (c) one or more variable heavy chains of (a) and one or morevariable light chains of (b).

In another embodiment, the variable heavy chain (V_(H)) has at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identitywith an amino acid sequence selected from the group consisting of SEQ IDNOS 36-409, and/or the variable light chain (V_(L)) has at least 70%,75%, 80%, 85%, 90%, 95%, 96%, 97%. 98% or 99% sequence identity with anamino acid sequence selected from the group consisting of SEQ ID NOS217-315.

In one aspect, also provided is an antigen binding protein thatspecifically binds to a linear or three-dimensional epitope comprisingone or more amino acid residues from FGFR1c, FGRF2c and FGFR3c.

In one aspect, also provided is an antigen binding protein thatspecifically binds to a linear or three-dimensional epitope comprisingone or more amino acid residues from β-Klotho.

In another aspect, also provided is an isolated antigen binding proteinthat specifically binds to a linear or three-dimensional epitopecomprising one or more amino acid residues from both β-Klotho and one ormore amino acid residues from FGFR1c, FGFR2c and FGFR3c.

In yet another embodiment, the isolated antigen binding proteindescribed hereinabove comprises a first amino acid sequence comprisingat least one of the CDRH consensus sequences disclosed herein, and asecond amino acid sequence comprising at least one of the CDRL consensussequences disclosed herein.

In one aspect, the first amino acid sequence comprises at least two ofthe CDRH consensus sequences, and/or the second amino acid sequencecomprises at least two of the CDRL consensus sequences. In certainembodiments, the first and the second amino acid sequence are covalentlybonded to each other.

In a further embodiment, the first amino acid sequence of the isolatedantigen binding protein comprises the CDRH3, the CDRH2 and the CDRH1parings shown in Table 5 for each clone, and/or the second amino acidsequence of the isolated antigen binding protein comprises the CDRL3,the CDRL2 and the CDRL1 pairings shown in Table 4 or each clone.

In a further embodiment, the antigen binding protein comprises at leasttwo CDRH sequences of heavy chain sequences H1, H2, H3, H4, H5, H6, H7,H8, H9, H10, H11, H12, H13, H14, H15, H16, H17 or H18, H19, H20, H21,H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32, H33, H34, H35,H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H146, H46, H48, H49,H50, H51, H52, H53, H54, H55, H56, H57, H58, H59, H60, H61, H62, H63,H64, H65, H66, H67, H68, H69, H70, H71, H72, H73, H74, H75, H76, H77,H78, H79, H80, H81, H82, H83, H84, H85, H86, H87, H88, H89, H90, H91,H92, H93 and H94, as shown in Tables 3A and 4A.

In again a further embodiment, the antigen binding protein comprises atleast two CDRL sequences of light chain sequences L1, L2, L3, L4, L5,L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20,L21, L22, L23, L24, L25, L26, L27, L28, L29, L30, L31, L32, L33, L34,L35, L36, L37, L38, L39, L40, L41, L42, L43, L44, L45, L46, L47, L48,L49, L50, L51, L52, L53, L54, L55, L56, L57, L58, L59, L60, L61, L62,L63, L64, L65, L66, L67, L68, L69, L70, L71, L72, L73, L74, L75, L76,L77, L78, L79, L80, L81, L82, L83, L84, L85, L86, L87, L88, L89, L90,L91, L92, L93, L94, L95, L96, L97, L98, L99 and L100, as shown in Tables3B and 4B.

In still a further embodiment, the antigen binding protein comprises atleast two CDRH sequences of heavy chain sequences H1, H2, H3, H4, H5,H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17 or H18, H19, H20,H21, H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32, H33, H34,H35, H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H146, H46, H48,H49, H50, H51, H52, H53, H54, H55, H56, H57, H58, H59, H60, H61, H62,H63, H64, H65, H66, H67, H68, H69, H70, H71, H72, H73, H74, H75, H76,H77, H78, H79, H80, H81, H82, H83, H84, H85, H86, H87, H88, H89, H90,H91, H92, H93 and H94, as shown in Tables 3A and 4A, and at least twoCDRLs of light chain sequences L1, L2, L3, L4, L5, L6, L7, L8, L9, L10,L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24,L25, L26, L27, L28, L29, L30, L31, L32, L33, L34, L35, L36, L37, L38,L39, L40, L41, L42, L43, L44, L45, L46, L47, L48, L49, L50, L51, L52,L53, L54, L55, L56, L57, L58, L59, L60, L61, L62, L63, L64, L65, L66,L67, L68, L69, L70, L71, L72, L73, L74, L75, L76, L77, L78, L79, L80,L81, L82, L83, L84, L85, L86, L87, L88, L89, L90, L91, L92, L93, L94,L95, L96, L97, L98, L99 and L100, as shown in Tables 3B and 4B.

In again another embodiment, the antigen binding protein comprises theCDRH1, CDRH2, and CDRH3 sequences of heavy chain sequences H1, H2, H3,H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17 or H18,H19, H20, H21, H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32,H33, H34, H35, H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H146,H46, H48, H49, H50, H51, H52, H53, H54, H55, H56, H57, H58, H59, H60,H61, H62, H63, H64, H65, H66, H67, H68, H69, H70, H71, H72, H73, H74,H75, H76, H77, H78, H79, H80, H81, H82, H83, H84, H85, H86, H87, H88,H89, H90, H91, H92, H93 and H94, as shown in Tables 3A and 4A.

In yet another embodiment, the antigen binding protein comprises theCDRL1, CDRL2, and CDRL3 sequences of light chain sequences L1, L2, L3,L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18,L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L29, L30, L31, L32,L33, L34, L35, L36, L37, L38, L39, L40, L41, L42, L43, L44, L45, L46,L47, L48, L49, L50, L51, L52, L53, L54, L55, L56, L57, L58, L59, L60,L61, L62, L63, L64, L65, L66, L67, L68, L69, L70, L71, L72, L73, L74,L75, L76, L77, L78, L79, L80, L81, L82, L83, L84, L85, L86, L87, L88,L89, L90, L91, L92, L93, L94, L95, L96, L97, L98, L99 and L100, as shownin Tables 3B and 4B.

In yet another embodiment, the antigen binding protein comprises all sixCDRs of an antigen binding protein comprising the following V_(H) andV_(L) pairs: V_(L)1 with V_(H)1; V_(L)2 with V_(H)1; V_(L)3 with V_(H)2or V_(H)3; V_(L)4 with V_(H)4; V_(L)5 with V_(H)5; V_(L)6 with V_(H)6;V_(L)7 with V_(H)6; V_(L)8 with V_(H)7 or V_(H)8; V_(L)9 with V_(H)9;V_(L)10 with V_(H)9; V_(L)11 with V_(H) 10; V_(L)12 with V_(H)11;V_(L)13 with V_(H)12; V_(L)13 with V_(H)14; V_(L)14 with V_(H)13;V_(L)15 with V_(H)14; V_(L)16 with V_(H)15; V_(L)17 with V_(H)16;V_(L)18 with V_(H)17; V_(L)19 with V_(H)18; V_(L)20 with V_(H)19;V_(L)21 with V_(H)20; V_(L)22 with V_(H)21; V_(L)23 with V_(H)22;V_(L)24 with V_(H)23; V_(L)25 with V_(H)24; V_(L)26 with V_(H)25;V_(L)27 with V_(H)26; V_(L)28 with V_(H)27; V_(L)29 with V_(H)28;V_(L)30 with V_(H)29; V_(L)31 with V_(H)30; V_(L)32 with V_(H)31;V_(L)33 with V_(H)32; V_(L)34 with V_(H)33; V_(L)35 with V_(H)34;V_(L)36 with V_(H)35; V_(L)37 with V_(H)36; V_(L)38 with V_(H)37;V_(L)39 with V_(H)38; V_(L)40 with V_(H)39; V_(L)41 with V_(H)40;V_(L)42 with V_(H)41; V_(L)43 with V_(H)42; V_(L)44 with V_(H)43;V_(L)45 with V_(H)44; V_(L)46 with V_(H)45; V_(L)47 with V_(H)46;V_(L)48 with V_(H)47; V_(L)49 with V_(H)48; V_(L)50 with V_(H)49;V_(L)51 with V_(H)50; V_(L)52 with V_(H)51; V_(L)53 with V_(H)52;V_(L)54 with V_(H)53; V_(L)55 with V_(H)54; V_(L)56 with V_(H)54;V_(L)57 with V_(H)54; V_(L)58 with V_(H)55; V_(L)59 with V_(H)56;V_(L)60 with V_(H)57; V_(L)61 with V_(H)58; V_(L)62 with V_(H)59;V_(L)63 with V_(H)60; V_(L)64 with V_(H)1; V_(L)65 with V_(H)62; V_(L)66with V_(H)63; V_(L)67 with V_(H)64; V_(L)68 with V_(H)65; V_(L)69 withV_(H)66; V_(L)70 with V_(H)67; V_(L)71 with V_(H)68; V_(L)72 withV_(H)69; V_(L)73 with V_(H)70; V_(L)74 with V_(H)70; V_(L)75 withV_(H)70; V_(L)76 with V_(H)71; V_(L)77 with V_(H)72; V_(L)78 withV_(H)73; V_(L)79 with V_(H)74; V_(L)80 with V_(H)75; V_(L)81 withV_(H)76; V_(L)82 with V_(H)77; V_(L)83 with V_(H)78; V_(L)84 withV_(H)79; V_(L)85 with V_(H)80; V_(L)86 with V_(H)81; V_(L)87 withV_(H)82; V_(L)88 with V_(H)86; V_(L)89 with V_(H)83; V_(L)90 withV_(H)84; V_(L)91 with V_(H)85; V_(L) 92 with V_(H) 87; V_(L) 93 withV_(H) 88; V_(L) 94 with V_(H) 88; V_(L) 95 with V_(H) 89; V_(L) 96 withV_(H) 90; V_(L) 97 with V_(H) 91; V_(L) 98 with V_(H) 92; V_(L) 99 withV_(H) 93; and V_(L) 100 with V_(H) 94; as shown in Tables 2A and 2B andTables 4A and 4B.

TABLE 7A Heavy Chain Sequences Full Heavy Full Heavy Variable HeavyVariable Heavy CDRH2 SEQ ID CDRH3 SEQ ID Ref (H#) SEQ ID NO (VH#) SEQ IDNO CDRH1 SEQ ID NO NO NO 63G8 H1 123 V_(H)1 326 636 667 782 68D3 64A867B4 64E6 H2 136 V_(H)2 339 637 699 783 65E8 65F11 67G7 63H11 H3 135V_(H)3 338 637 689 783 63B6 H4 133 V_(H)4 336 638 700 784 64D4 65C3 H5142 V_(H)5 345 626 701 785 68D5 63E6 H6 113 V_(H)6 316 639 702 786 66F764H5 H7 126 V_(H)7 329 614 703 787 65G4 H8 129 V_(H)8 332 614 703 78767G10v1 H9 121 V_(H)9 324 640 704 788 67G10v2 66B4 H10 115 V_(H)10 318617 708 791 66G2 H11 124 V_(H)11 327 614 709 782 68G5 H12 130 V_(H)12333 614 710 792 63F5 H13 134 V_(H)13 337 637 705 783 66F6 H14 138V_(H)14 341 637 689 783 65C1 H15 137 V_(H)15 340 637 707 790 64A7 H16141 V_(H)16 344 642 706 789 66D4 H17 114 V_(H)17 317 645 711 793 65B1H18 116 V_(H)18 319 646 712 794 67A4 H19 118 V_(H)19 321 647 713 79565B4 H20 117 V_(H)20 320 648 714 796 63A10 H21 119 V_(H)21 322 640 715788 65H11 H22 120 V_(H)22 323 640 716 788 64C8 H23 122 V_(H)23 325 614717 797 65E3 H24 128 V_(H)24 331 649 718 798 65D4 H25 127 V_(H)25 330650 677 799 65D1 H26 125 V_(H)26 328 651 719 800 67G8 H27 131 V_(H)27334 614 720 801 65B7 H28 132 V_(H)28 335 652 707 802 64A6 H29 139V_(H)29 342 616 721 803 65F9 H30 140 V_(H)30 343 638 689 804 67F5 H31143 V_(H)31 346 626 722 785 64B10 H32 144 V_(H)32 347 638 723 805 68C8H33 145 V_(H)33 348 653 724 806 67A5 H34 146 V_(H)34 349 627 686 80767C10 H35 147 V_(H)35 350 627 686 808 64H6 H36 148 V_(H)36 351 627 725809 63F9 H37 149 V_(H)37 352 654 726 810 67F6 H38 150 V_(H)38 353 655686 811 48H11 H39 154 V_(H)39 357 606 659 736 52A8 H40 164 V_(H)40 368617 672 749 52F8 H41 167 V_(H)41 371 619 675 753 49H12 H42 159 V_(H)42362 612 665 742 54A1 H43 172 V_(H)43 376 612 680 742 55G9 49C8 H44 156V_(H)44 359 609 662 739 52H1 60G5.2 H45 193 V_(H)45 397 635 697 780 49G3H46 158 V_(H)46 361 611 664 741 59A10 H47 187 V_(H)47 391 632 692 77349H4 48F8 H48 153 V_(H)48 356 605 658 735 53B9 56B4 57E7 57F11 59C9 H49188 V_(H)49 392 633 693 774 58A5 57A4 57F9 51G2 H50 163 V_(H)50 367 605671 748 56A7 H51 179 V_(H)51 383 605 671 764 56E4 54H10 H52 173 V_(H)52377 623 681 759 55D1 48H3 53C11 59G10.3 H53 190 V_(H)53 394 634 695 77759D10v1 H54 195 V_(H)54 364 615 668 745 59D10v2 51C10.1 60F9 H55 192V_(H)55 396 623 696 779 48B4 52D6 61G5 H56 194 V_(H)56 398 623 698 78159G10.2 H57 189 V_(H)57 393 608 694 776 51A8 H58 160 V_(H)58 363 614 667744 53H5.2 H59 170 V_(H)59 374 614 678 756 53F6 H60 169 V_(H)60 373 621677 755 56C11 H61 180 V_(H)61 384 614 685 765 49A10 H62 155 V_(H)62 358608 661 738 48D4 49G2 H63 157 V_(H)63 360 610 663 740 50C12 55G11 52C1H64 166 V_(H)64 370 614 674 751 55E9 H65 176 V_(H)65 380 625 683 76260D7 H66 191 V_(H)66 395 614 677 778 51C10.2 H67 161 V_(H)67 365 616 669746 55D3 H68 174 V_(H)68 378 624 682 760 57B12 H69 184 V_(H)69 388 630689 760 55E4 H70 175 V_(H)70 379 604 656 752 52C5 60G5.1 55E4 49B1150H10 53C1 56G1 H71 182 V_(H)71 386 604 656 752 48F3 H72 152 V_(H)72 355604 657 734 48C9 H73 151 V_(H)73 354 603 656 733 49A12 51E2 51E5 H74 162V_(H)74 366 604 670 747 53H5.3 H75 171 V_(H)75 375 622 679 757 56G3.3H76 183 V_(H)76 387 629 688 769 55B10 52B8 H77 165 V_(H)77 369 618 673750 55G5 H78 177 V_(H)78 381 626 684 763 52H2 H79 168 V_(H)79 372 620676 754 56G3.2 H80 196 V_(H)80 399 628 687 768 56E7 H81 181 V_(H)81 385627 686 766 57D9 H82 185 V_(H)82 389 631 690 771 48G4 H83 197 V_(H)83400 607 660 737 53C3.1 50G1 H84 178 V_(H)84 382 613 666 743 58C2 H85 186V_(H)85 390 608 691 772 61H5 H86 198 V_(H)86 401 629 727 769 52B9 50D4H87 199 V_(H)87 402 643 730 812 50G5v1 H88 200 V_(H)88 403 639 728 76750G5v2 51C1 H89 201 V_(H)89 404 604 656 752 53C3.2 H90 202 V_(H)90 405641 732 775 54H10.3 H91 203 V_(H)91 406 645 729 813 55A7 H92 204 V_(H)92407 626 673 770 55E6 H93 205 V_(H)93 408 605 731 761 61E1 H94 206V_(H)94 409 644 690 758

TABLE 7B Light Chain Sequences Full Light Full Light Variable LightVariable Light SEQ CDRL1 SEQ ID CDRL2 SEQ ID CDRL3 SEQ ID Ref (L#) SEQID NO (VH#) ID NO NO NO NO 63G8 L1 26 V_(L)1 229 826 922 987 64A8 67B468D3 L2 28 V_(L)2 231 826 922 987 65E8 L3 37 V_(L)3 241 859 927 98863H11 64E6 67G7 65F11 63B6 L4 35 V_(L)4 239 860 928 989 64D4 65C3 L5 43V_(L)5 247 861 929 990 68D5 63E6 L6 14 V_(L)6 217 862 907 991 66F7 L7 15V_(L)7 218 863 907 991 64H5 L8 30 V_(L)8 233 864 930 992 65G4 67G10v1 L923 V_(L)9 226 865 931 993 67G10v2 L10 24 V_(L)10 227 866 932 994 66B4L11 17 V_(L)11 220 870 933 996 66G2 L12 27 V_(L)12 230 835 934 997 68G5L13 100 V_(L)13 236 872 935 998 63F5 L14 36 V_(L)14 240 867 913 988 66F6L15 39 V_(L)15 243 859 928 988 65C1 L16 38 V_(L)16 242 869 928 988 64A7L17 42 V_(L)17 246 868 913 995 66D4 L18 16 V_(L)18 219 873 907 999 65B1L19 18 V_(L)19 221 874 936 961 67A4 L20 20 V_(L)20 223 875 918 1001 65B4L21 19 V_(L)21 222 876 918 1001 63A10 L22 21 V_(L)22 224 865 938 100265H11 L23 22 V_(L)23 225 878 931 1003 64C8 L24 25 V_(L)24 228 879 9401004 65E3 L25 32 V_(L)25 235 864 935 1005 65D4 L26 31 V_(L)26 234 880935 1006 65D1 L27 29 V_(L)27 232 852 925 1007 67G8 L28 33 V_(L)28 237882 930 1005 65B7 L29 34 V_(L)29 238 883 913 1008 64A6 L30 40 V_(L)30244 884 941 1009 65F9 L31 41 V_(L)31 245 885 908 1009 67F5 L32 44V_(L)32 248 885 942 1010 64B10 L33 45 V_(L)33 249 886 943 963 68C8 L3446 V_(L)34 250 887 909 963 67A5 L35 47 V_(L)35 251 888 898 1012 67C10L36 48 V_(L)36 252 888 898 951 64H6 L37 49 V_(L)37 253 864 930 1014 63F9L38 50 V_(L)38 254 889 944 1015 67F6 L39 51 V_(L)39 255 890 945 95148H11 L40 55 V_(L)40 259 817 897 950 52A8 L41 66 V_(L)41 270 828 907 96152F8 L42 69 V_(L)42 273 832 910 965 49H12 L43 60 V_(L)43 264 822 901 95554A1 L44 74 V_(L)44 278 837 899 955 55G9 49C8 L45 57 V_(L)45 261 819 899952 52H1 60G5.2 L46 93 V_(L)46 297 857 925 986 49G3 L47 59 V_(L)47 263821 900 954 59A10 L48 87 V_(L)48 291 827 921 960 49H4 48F8 L49 54V_(L)49 258 816 896 949 53B9 56B4 57E7 57F11 59C9 L50 88 V_(L)50 292 850922 960 58A5 57A4 57F9 51G2 L51 65 V_(L)51 269 827 906 960 56A7 L52 80V_(L)52 284 842 917 960 56E4 54H10.1 L53 75 V_(L)53 279 838 913 970 55D148H3 53C11 59G10.3 L54 90 V_(L)54 294 854 909 983 51C10.1 L55 62 V_(L)55266 824 903 957 59D10v1 L56 97 V_(L)56 301 851 903 980 59D10v2 L57 98V_(L)57 302 852 923 981 60F9 L58 92 V_(L)58 296 856 924 985 48B4 52D661G5 L59 94 V_(L)59 298 858 926 985 59G10.2 L60 89 V_(L)60 293 853 904982 51A8 L61 61 V_(L)61 265 823 902 956 53H5.2 L62 72 V_(L)62 276 835907 968 53F6 L63 71 V_(L)63 275 834 912 967 56C11 L64 81 V_(L)64 285 843918 974 49A10 L65 56 V_(L)65 260 818 898 951 48D4 49G2 L66 58 V_(L)66262 820 898 953 50C12 55G11 52C1 L67 68 V_(L)67 272 830 909 963 55E9 L6878 V_(L)68 282 840 910 972 60D7 L69 91 V_(L)69 295 820 898 984 51C10.2L70 63 V_(L)70 267 825 904 958 55D3 L71 76 V_(L)71 280 839 907 971 57B12L72 85 V_(L)72 289 847 907 978 52C5 L73 95 V_(L)73 299 831 907 96460G5.1 L74 V_(L)74 55E4 L75 77 V_(L)75 281 831 914 964 49B11 50H10 53C156G1 L76 83 V_(L)76 287 831 907 976 48F3 L77 53 V_(L)77 257 815 895 94848C9 L78 52 V_(L)78 256 814 894 947 49A12 51E2 51E5 L79 64 V_(L)79 268826 905 959 53H5.3 L80 73 V_(L)80 277 836 908 969 56G3.3 L81 84 V_(L)81288 846 920 977 55B10 52B8 L82 67 V_(L)82 271 829 908 962 55G5 L83 79V_(L)83 283 841 916 973 52H2 L84 70 V_(L)84 274 833 911 966 56G3.2 L8599 V_(L)85 303 845 919 962 56E7 L86 82 V_(L)86 286 844 900 975 57D9 L8786 V_(L)87 290 848 913 976 61H5 L88 96 V_(L)88 300 846 913 977 52B9 48G4L89 101 V_(L)89 304 892 928 1017 53C3.1 50G1 L90 102 V_(L)90 305 820 898984 58C2 L91 103 V_(L)91 306 893 898 1012 50D4 L92 104 V_(L)92 307 839946 1019 50G5v1 L93 105 V_(L)93 308 835 907 1018 50G5v2 L94 106 V_(L)94309 891 915 1020 51C1 L95 107 V_(L)95 310 831 907 964 53C3.2 L96 108V_(L)96 311 849 937 1016 54H10.3 L97 109 V_(L)97 312 855 939 999 55A7L98 110 V_(L)98 313 871 907 1000 55E6 L99 111 V_(L)99 314 877 913 101161E1 L100 112 V_(L)100 315 881 907 1013

In one aspect, the isolated antigen binding proteins that specificallybind to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c provided herein can be a monoclonalantibody, a polyclonal antibody, a recombinant antibody, a humanantibody, a humanized antibody, a chimeric antibody, a multispecificantibody, or an antibody fragment thereof.

In another embodiment, the antibody fragment of the isolatedantigen-binding proteins provided herein can be a Fab fragment, a Fab′fragment, an F(ab)₂ fragment, an Fv fragment, a diabody, or a singlechain antibody molecule.

In a further embodiment, an isolated antigen binding protein thatspecifically binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c provided herein is a humanantibody and can be of the IgG1-, IgG2-IgG3- or IgG4-type.

In another embodiment, an isolated antigen binding protein thatspecifically binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c comprises a light or a heavychain polypeptide as set forth in Tables 1A-1B. In some embodiments, anantigen binding protein that specifically binds to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3ccomprises a variable light or variable heavy domain such as those listedin Tables 2A-2B. In still other embodiments, an antigen binding proteinthat specifically binds to a complex comprising β-Klotho and at leastone of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c comprises one, two orthree CDRHs or one, two or three CDRLs as set forth in Tables 3A-3B,4A-4B, infra. Such antigen binding proteins, and indeed any of theantigen binding proteins disclosed herein, can be PEGylated with one ormore PEG molecules, for examples PEG molecules having a molecular weightselected from the group consisting of 5K, 10K, 20K, 40K, 50K, 60K, 80K,100K or greater than 100K.

In yet another aspect, any antigen binding protein that specificallybinds to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c provided herein can be coupled to alabeling group and can compete for binding to the extracellular portionof the individual protein components of a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with anantigen binding protein of one of the isolated antigen binding proteinsprovided herein. In one embodiment, the isolated antigen binding proteinprovided herein can reduce blood glucose levels, decrease triglycerideand cholesterol levels or improve other glycemic parameters andcardiovascular risk factors when administered to a patient.

As will be appreciated, for any antigen binding protein comprising morethan one CDR provided in Tables 3A-3B, and 4A-4B, any combination ofCDRs independently selected from the depicted sequences may be useful.Thus, antigen binding proteins with one, two, three, four, five or sixof independently selected CDRs can be generated. However, as will beappreciated by those in the art, specific embodiments generally utilizecombinations of CDRs that are non-repetitive, e.g., antigen bindingproteins are generally not made with two CDRH2 regions, etc.

Some of the antigen binding proteins that specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c that are provided herein are discussed in more detailbelow.

Antigen Binding Proteins and Binding Epitopes and Binding Domains

When an antigen binding protein is said to bind an epitope on a complexβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c,or the extracellular domain of a protein component of such a complex,what is meant is that the antigen binding protein specifically binds toa specified portion of the complex comprising β-Klotho and an FGFR(e.g., FGFR1c, FGFR2c or FGFR3c) or to the extracellular domain of sucha complex. In some embodiments, e.g., in certain cases where the antigenbinding protein binds only β-Klotho, the antigen binding protein canspecifically bind to a polypeptide consisting of specified residues(e.g., a specified segment of β-Klotho). In other embodiments, e.g., incertain cases where an antigen binding protein interacts with bothβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c,the antigen binding protein can bind residues, sequences of residues, orregions in both β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c, depending on which receptor the antigen binding proteinrecognizes. In still other embodiments the antigen binding protein willbind residues, sequences or residues or regions of a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c,for example FGFR1c.

In any of the foregoing embodiments, such an antigen binding proteindoes not need to contact every residue of β-Klotho or a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c, or the extracellular domain of the recited proteins orcomplexes. Nor does every single amino acid substitution or deletionwithin β-Klotho or a complex comprising β-Klotho and at least one of (i)FGFR1c, (ii) FGFR2c and (iii) FGFR3c, or the extracellular domain of therecited proteins or complexes, necessarily significantly affect bindingaffinity.

Epitope specificity and the binding domain(s) of an antigen bindingprotein can be determined by a variety of methods. Some methods, forexample, can use truncated portions of an antigen. Other methods utilizeantigen mutated at one or more specific residues, such as by employingan alanine scanning or arginine scanning-type approach or by thegeneration and study of chimeric proteins in which various domains,regions or amino acids are swapped between two proteins (e.g., mouse andhuman forms of one or more of the antigens or target proteins), or byprotease protection assays.

Competing Antigen Binding Proteins

In another aspect, antigen binding proteins are provided that competewith one of the exemplified antibodies or functional fragments forbinding to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c. Such antigen binding proteins can alsobind to the same epitope as one of the herein exemplified antigenbinding proteins, or an overlapping epitope. Antigen binding proteinsand fragments that compete with or bind to the same epitope as theexemplified antigen binding proteins are expected to show similarfunctional properties. The exemplified antigen binding proteins andfragments include those with the heavy and light chains H1-H94 andL1-L100, variable region domains V_(L)1-V_(L)100 and V_(H)1-V_(H)94, andCDRs provided herein, including those in Tables 1, 2, 3, and 4. Thus, asa specific example, the antigen binding proteins that are providedinclude those that compete with an antibody comprising:

(a) 1, 2, 3, 4, 5 or all 6 of the CDRs listed for an antigen bindingprotein listed in Tables 3A and 3B, and 4A and 4B, infra;

(b) a V_(H) and a V_(L) selected from V_(L)1-V_(L)100 and V_(H)1-V_(H)94and listed for an antigen binding protein listed in Tables 2A and 2B; or

(c) two light chains and two heavy chains as specified for an antigenbinding protein listed in Tables 1A and 1B, infra.

Thus, in one embodiment, the present disclosure provides antigen bindingproteins, including human antibodies, that competes for binding to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c with a reference antibody, wherein the referenceantibody comprises a combination of light chain and heavy chain variabledomain sequences selected from the group consisting of V_(L)1 withV_(H)1, V_(L)2 with V_(H)1, V_(L)3 with V_(H)2 or V_(H)3, V_(L)4 withV_(H)4, V_(L)5 with V_(H)5, V_(L)6 with V_(H)6, V_(L)7 with V_(H)6,V_(L)8 with V_(H)7 or V_(H)8, V_(L)9 with V_(H)9, V_(L)10 with V_(H)9,V_(L)11 with V_(H) 10, V_(L)12 with V_(H)11, V_(L)13 with V_(H)12,V_(L)13 with V_(H)14, V_(L)14 with V_(H)13, V_(L)15 with V_(H)14,V_(L)16 with V_(H)15, V_(L)17 with V_(H)16, V_(L)18 with V_(H)17,V_(L)19 with V_(H)18, V_(L)20 with V_(H)19, V_(L)21 with V_(H)20,V_(L)22 with V_(H)21, V_(L)23 with V_(H)22, V_(L)24 with V_(H)23,V_(L)25 with V_(H)24, V_(L)26 with V_(H)25, V_(L)27 with V_(H)26,V_(L)28 with V_(H)27, V_(L)29 with V_(H)28, V_(L)30 with V_(H)29,V_(L)31 with V_(H)30, V_(L)32 with V_(H)31, V_(L)33 with V_(H)32,V_(L)34 with V_(H)33, V_(L)35 with V_(H)34, V_(L)36 with V_(H)35,V_(L)37 with V_(H)36, V_(L)38 with V_(H)37, V_(L)39 with V_(H)38,V_(L)40 with V_(H)39, V_(L)41 with V_(H)40, V_(L)42 with V_(H)41,V_(L)43 with V_(H)42, V_(L)44 with V_(H)43, V_(L)45 with V_(H)44,V_(L)46 with V_(H)45, V_(L)47 with V_(H)46, V_(L)48 with V_(H)47,V_(L)49 with V_(H)48, V_(L)50 with V_(H)49, V_(L)51 with V_(H)50, 52with V_(H)51, V_(L)53 with V_(H)52, V_(L)54 with V_(H)53, V_(L)55 with54, and V_(L)56 with V_(H)54, V_(L)57 with V_(H)54, V_(L)58 withV_(H)55, V_(L)59 with V_(H)56, V_(L)60 with V_(H)57, V_(L)61 withV_(H)58, V_(L)62 with V_(H)59, V_(L)63 with V_(H)60, V_(L)64 withV_(H)1, V_(L)65 with V_(H)62, V_(L)66 with V_(H)63, V_(L)67 withV_(H)64, V_(L)68 with V_(H)65, V_(L)69 with V_(H)66, V_(L)70 withV_(H)67, V_(L)71 with V_(H)68, V_(L)72 with V_(H)69, V_(L)73 withV_(H)70, V_(L)74 with V_(H)70, and V_(L)75 with V_(H)70, V_(L)76 withV_(H)71, V_(L)77 with V_(H)72, V_(L)78 with V_(H)73, V_(L)79 withV_(H)74, V_(L)80 with V_(H)75, V_(L)81 with V_(H)76, V_(L)82 withV_(H)77, V_(L)83 with V_(H)78, V_(L)84 with V_(H)79, V_(L)85 withV_(H)80, V_(L)86 with V_(H)81, V_(L)87 with V_(H)82, V_(L)88 withV_(H)86, V_(L)89 with V_(H)83, V_(L)90 with V_(H)84, V_(L)91 withV_(H)85, V_(L) 92 with V_(H) 87, V_(L) 93 with V_(H) 88, V_(L) 94 withV_(H) 88, V_(L) 95 with V_(H) 89, V_(L) 96 with V_(H) 90, V_(L) 97 withV_(H) 91, V_(L) 98 with V_(H) 92, V_(L) 99 with V_(H) 93, and V_(L) 100with V_(H) 94.

In another embodiment, the present disclosure provides antigen bindingproteins, including human antibodies, that compete for binding to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c with a reference antibody, wherein the referenceantibody is 63G8, 64A8, 67B4, 68D3, 64E6, 65E8, 65F11, 67G7, 63B6, 64D4,65C3, 68D5, 63E6, 66F7, 64H5, 65G4, 67G10v1, 67G10v2, 66B4, 66G2, 68G5,63F5, 66F6, 65C1, 64A7, 66D4, 65B1, 67A4, 65B4, 63A10, 65H11, 64C8,65E3, 65D4, 65D1, 67G8, 65B7, 64A6, 65F9, 67F5, 64B10, 68C8, 67A5,67C10, 64H6, 63F9, 67F6, 48H11, 52A8, 52F8, 49H12, 54A1, 55G9, 49C8,52H1, 60G5.2, 49G3, 59A10, 48F8, 53B9, 56B4, 57E7, 57F11, 59C9, 58A5,57A4, 57F9, 51G2, 56A7, 56E4, 54H10, 55D1, 48H3, 53C11, 59G10.3,51C10.1, 59D10v1, 59D10v2, 60F9, 48B4, 52D6, 61G5, 59G10.2, 51A8,53H5.2, 53F6, 56C11, 49A10, 48D4, 49G2, 50C12, 55G11, 52C1, 55E9, 60D7,51C10.2, 55D3, 57B12, 52C5, 60G5.1, 55E4, 49B11, 50H10, 53C1, 56G1,48F3, 48C9, 49A12, 51E2, 51E5, 53H5.3, 56G3.3, 55B10, 52B8, 55G5, 52H2,56G3.2, 6E7, 57D9, 61H5, 48G4, 50G1, 58C2, 50D4, 50G5v1, 50G5v2, 51C1,53C3.2, 54H10.3, 55A7, 55E6, 61E1, 53C3.1, 49H4, and 51E2.

In a further embodiment, an isolated antigen binding protein, such as ahuman antibody, is provided that binds to a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c withsubstantially the same Kd as a reference antibody; initiates FGF21-likesignaling in an in vitro ELK-Luciferase assay to the same degree as areference antibody; lowers blood glucose; lowers serum lipid levels;and/or competes for binding with said reference antibody to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c, wherein the reference antibody is selected from the groupconsisting of 63G8, 64A8, 67B4, 68D3, 64E6, 65E8, 65F11, 67G7, 63B6,64D4, 65C3, 68D5, 63E6, 66F7, 64H5, 65G4, 67G10v1, 67G10v2, 66B4, 66G2,68G5, 63F5, 66F6, 65C1, 64A7, 66D4, 65B1, 67A4, 65B4, 63A10, 65H11,64C8, 65E3, 65D4, 65D1, 67G8, 65B7, 64A6, 65F9, 67F5, 64B10, 68C8, 67A5,67C10, 64H6, 63F9, 67F6, 48H11, 52A8, 52F8, 49H12, 54A1, 55G9, 49C8,52H1, 60G5.2, 49G3, 59A10, 48F8, 53B9, 56B4, 57E7, 57F11, 59C9, 58A5,57A4, 57F9, 51G2, 56A7, 56E4, 54H10, 55D1, 48H3, 53C11, 59G10.3,51C10.1, 59D10v1, 59D10v2, 60F9, 48B4, 52D6, 61G5, 59G10.2, 51A8,53H5.2, 53F6, 56C11, 49A10, 48D4, 49G2, 50C12, 55G11, 52C1, 55E9, 60D7,51C10.2, 55D3, 57B12, 52C5, 60G5.1, 55E4, 49B11, 50H10, 53C1, 56G1,48F3, 48C9, 49A12, 51E2, 51E5, 53H5.3, 56G3.3, 55B10, 52B8, 55G5, 52H2,56G3.2, 6E7, 57D9, 61H5, 48G4, 50G1, 58C2, 50D4, 50G5v1, 50G5v2, 51C1,53C3.2, 54H10.3, 55A7, 55E6, 61E1, 53C3.1, 49H4, and 51E2.

The ability to compete with an antibody can be determined using anysuitable assay, such as those described herein, in which antigen bindingproteins 63G8, 64A8, 67B4, 68D3, 64E6, 65E8, 65F11, 67G7, 63B6, 64D4,65C3, 68D5, 63E6, 66F7, 64H5, 65G4, 67G10v1, 67G10v2, 66B4, 66G2, 68G5,63F5, 66F6, 65C1, 64A7, 66D4, 65B1, 67A4, 65B4, 63A10, 65H11, 64C8,65E3, 65D4, 65D1, 67G8, 65B7, 64A6, 65F9, 67F5, 64B10, 68C8, 67A5,67C10, 64H6, 63F9, 67F6, 48H11, 52A8, 52F8, 49H12, 54A1, 55G9, 49C8,52H1, 60G5.2, 49G3, 59A10, 48F8, 53B9, 56B4, 57E7, 57F11, 59C9, 58A5,57A4, 57F9, 51G2, 56A7, 56E4, 54H10, 55D1, 48H3, 53C11, 59G10.3,51C10.1, 59D10v1, 59D10v2, 60F9, 48B4, 52D6, 61G5, 59G10.2, 51A8,53H5.2, 53F6, 56C11, 49A10, 48D4, 49G2, 50C12, 55G11, 52C1, 55E9, 60D7,51C10.2, 55D3, 57B12, 52C5, 60G5.1, 55E4, 49B11, 50H10, 53C1, 56G1,48F3, 48C9, 49A12, 51E2, 51E5, 53H5.3, 56G3.3, 55B10, 52B8, 55G5, 52H2,56G3.2, 6E7, 57D9, 61H5, 48G4, 50G1, 58C2, 50D4, 50G5v1, 50G5v2, 51C1,53C3.2, 54H10.3, 55A7, 55E6, 61E1, 53C3.1, 49H4, and 51E2 can be used asthe reference antibody.

Monoclonal Antibodies

The antigen binding proteins that are provided include monoclonalantibodies that bind to a complex comprising β-Klotho and at least oneof (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, and induce FGF21-likesignaling to various degrees. Monoclonal antibodies can be producedusing any technique known in the art, e.g., by immortalizing spleencells harvested from the transgenic animal after completion of theimmunization schedule. The spleen cells can be immortalized using anytechnique known in the art, e.g., by fusing them with myeloma cells toproduce hybridomas. Myeloma cells for use in hybridoma-producing fusionprocedures preferably are non-antibody-producing, have high fusionefficiency, and enzyme deficiencies that render them incapable ofgrowing in certain selective media which support the growth of only thedesired fused cells (hybridomas). Examples of suitable cell lines foruse in mouse fusions include Sp-20, P3-X63/Ag8, P3-X63-Ag8.653, NS1/1.Ag4 1, Sp210-Ag14, FO, NSO/U, MPC-11, MPC11-X45-GTG 1.7 and S194/5XXO Bul;examples of cell lines used in rat fusions include R210.RCY3, Y3-Ag1.2.3, IR983F and 4B210. Other cell lines useful for cell fusions areU-266, GM1500-GRG2, LICR-LON-HMy2 and UC729-6.

In some instances, a hybridoma cell line is produced by immunizing ananimal (e.g., a transgenic animal having human immunoglobulin sequences)with an immunogen comprising (1) cell-bound receptor of CHOtransfectants expressing full length human FGFR1c and β-Klotho at thecell surface, obtained by transfecting CHO cells with cDNA encoding ahuman full length FGFR1c polypeptide of SEQ ID NO: 4 and cDNA encoding ahuman β-Klotho polypeptide of SEQ ID NO: 7 with cells incubated withFGF21 prior to freezing (as shown in Example 2); or (2) cell-boundreceptor of 293T transfectants expressing full length human β-Klotho andan N-terminal truncated form of human FGFR1c encompassing amino acidresidue #141 to #822 polypeptide of SEQ ID NO: 4 (as shown in Example2); harvesting spleen cells from the immunized animal; fusing theharvested spleen cells to a myeloma cell line, thereby generatinghybridoma cells; establishing hybridoma cell lines from the hybridomacells, and identifying a hybridoma cell line that produces an antibodythat binds to a complex comprising β-Klotho and at least one of (i)FGFR1c, (ii) FGFR2c and (iii) FGFR3c and can induce FGF21-like signaling(e.g., as described in Example 4). Such hybridoma cell lines, and themonoclonal antibodies produced by them, form aspects of the presentdisclosure.

Monoclonal antibodies secreted by a hybridoma cell line can be purifiedusing any technique known in the art. Hybridomas or mAbs can be furtherscreened to identify mAbs with particular properties, such as theability to induce FGF21-like signaling. Examples of such screens areprovided herein.

Chimeric and Humanized Antibodies

Chimeric and humanized antibodies based upon the foregoing sequences canreadily be generated. One example is a chimeric antibody, which is anantibody composed of protein segments from different antibodies that arecovalently joined to produce functional immunoglobulin light or heavychains or immunologically functional portions thereof. Generally, aportion of the heavy chain and/or light chain is identical with orhomologous to a corresponding sequence in antibodies derived from aparticular species or belonging to a particular antibody class orsubclass, while the remainder of the chain(s) is/are identical with orhomologous to a corresponding sequence in antibodies derived fromanother species or belonging to another antibody class or subclass. Formethods relating to chimeric antibodies, see, for example, U.S. Pat. No.4,816,567; and Morrison et al., (1985) Proc. Natl. Acad. Sci. USA81:6851-6855, which are hereby incorporated by reference. CDR graftingis described, for example, in U.S. Pat. No. 6,180,370, U.S. Pat. No.5,693,762, U.S. Pat. No. 5,693,761, U.S. Pat. No. 5,585,089, and U.S.Pat. No. 5,530,101.

Generally, a goal of making a chimeric antibody is to create a chimerain which the number of amino acids from the intended patient/recipientspecies is maximized. One example is the “CDR-grafted” antibody, inwhich the antibody comprises one or more complementarity determiningregions (CDRs) from a particular species or belonging to a particularantibody class or subclass, while the remainder of the antibody chain(s)is/are identical with or homologous to a corresponding sequence inantibodies derived from another species or belonging to another antibodyclass or subclass. For use in humans, the variable region or selectedCDRs from a rodent antibody often are grafted into a human antibody,replacing the naturally-occurring variable regions or CDRs of the humanantibody.

One useful type of chimeric antibody is a “humanized” antibody.Generally, a humanized antibody is produced from a monoclonal antibodyraised initially in a non-human animal. Certain amino acid residues inthis monoclonal antibody, typically from non-antigen recognizingportions of the antibody, are modified to be homologous to correspondingresidues in a human antibody of corresponding isotype. Humanization canbe performed, for example, using various methods by substituting atleast a portion of a rodent variable region for the correspondingregions of a human antibody (see, e.g., U.S. Pat. No. 5,585,089, andU.S. Pat. No. 5,693,762; Jones et al., (1986) Nature 321:522-525;Riechmann et al., (1988) Nature 332:323-27; Verhoeyen et al., (1988)Science 239:1534-1536).

In one aspect, the CDRs of the light and heavy chain variable regions ofthe antibodies provided herein (e.g., in Tables 3-4 and 21-23) aregrafted to framework regions (FRs) from antibodies from the same, or adifferent, phylogenetic species. For example, the CDRs of the heavy andlight chain variable regions V_(H)1, V_(H)2, V_(H)3, V_(H)4, V_(H)5,V_(H)6, V_(H)7, V_(H)8, V_(H)9, V_(H)10, V_(H)11, V_(H)12, V_(H)13,V_(H)14, V_(H)15, V_(H)16, V_(H)17, V_(H)18, V_(H)19, V_(H)20, V_(H)21V_(H)22, V_(H)23, V_(H)24, V_(H)25, V_(H)26, V_(H)27, V_(H)28, V_(H)29,V_(H)30, V_(H)31, V_(H)32, V_(H)33, V_(H)34, V_(H)35, V_(H)36, V_(H)37,V_(H)38, V_(H)39, V_(H)40, V_(H)41, V_(H)42, V_(H)43, V_(H)44, V_(H)45,V_(H)46, V_(H)47, V_(H)48, V_(H)49, V_(H)50, V_(H)51, V_(H)52, V_(H)53,V_(H)54, V_(H)55, V_(H)56, V_(H)57, V_(H)58, V_(H)59, V_(H)60, V_(H)61,V_(H)62, V_(H)63, V_(H)64, V_(H)65, V_(H)66, V_(H)67, V_(H)68, V_(H)69,V_(H)70, V_(H)71, V_(H)72, V_(H)73, V_(H)74, V_(H)75, V_(H)76, V_(H)77,V_(H)78, V_(H)79, V_(H)80, 81, V_(H)82, V_(H)83, V_(H)84, V_(H)85, V_(H)86, V_(H) 87, V_(H)88, V_(H)89, V_(H)90, V_(H)91, V_(H)92, V_(H)93, andV_(H)94 and/or V_(L)1, V_(L)2, V_(L)3, V_(L)4, V_(L)5, V_(L)6, V_(L)7,V_(L)8, V_(L)9, V_(L)10, V_(L)11, V_(L)12, V_(L)13, V_(L)14, V_(L)15,V_(L)16, V_(L)17, V_(L)18, V_(L)19, V_(L)20, V_(L)21, V_(L)22, V_(L)23,V_(L)24, V_(L)25, V_(L)26, V_(L)27, V_(L)28, V_(L)29, V_(L)30, V_(L)31,V_(L)32, V_(L)33, V_(L)34, V_(L)35, V_(L)36, V_(L)37, V_(L)38, V_(L)39,V_(L)40, V_(L)41, V_(L)42, V_(L)43, V_(L)44, V_(L)45, V_(L)46, V_(L)47,V_(L)48, V_(L)49, V_(L)50, V_(L)51, V_(L)52, V_(L)53, V_(L)54, V_(L)55,V_(L)56, V_(L)57, V_(L)58, V_(L)59, V_(L)60, V_(L)61, V_(L)62, V_(L)63,V_(L)64, V_(L)65, V_(L)66, V_(L)67, V_(L)68, V_(L)69, V_(L)70, V_(L)71,V_(L)72, V_(L)73, V_(L)74, V_(L)75, V_(L)76, V_(L)77, V_(L)78, V_(L)79,V_(L)80, V_(L)81, V_(L)82, V_(L)83, V_(L)84, V_(L)85, V_(L)86, V_(L)87,V_(L)88, V_(L)89, V_(L)90, V_(L)91, V_(L)92, V_(L)93, V_(L)94, V_(L)95,V_(L)96, V_(L)97, V_(L)98, V_(L)99 and V_(L)100 can be grafted toconsensus human FRs. To create consensus human FRs, FRs from severalhuman heavy chain or light chain amino acid sequences can be aligned toidentify a consensus amino acid sequence. In other embodiments, the FRsof a heavy chain or light chain disclosed herein are replaced with theFRs from a different heavy chain or light chain. In one aspect, rareamino acids in the FRs of the heavy and light chains of an antigenbinding protein (e.g., an antibody) that specifically binds to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c are not replaced, while the rest of the FR amino acids arereplaced. A “rare amino acid” is a specific amino acid that is in aposition in which this particular amino acid is not usually found in anFR. Alternatively, the grafted variable regions from the one heavy orlight chain can be used with a constant region that is different fromthe constant region of that particular heavy or light chain as disclosedherein. In other embodiments, the grafted variable regions are part of asingle chain Fv antibody.

In certain embodiments, constant regions from species other than humancan be used along with the human variable region(s) to produce hybridantibodies.

Fully Human Antibodies

Fully human antibodies are provided by the instant disclosure. Methodsare available for making fully human antibodies specific for a givenantigen without exposing human beings to the antigen (“fully humanantibodies”). One specific means provided for implementing theproduction of fully human antibodies is the “humanization” of the mousehumoral immune system. Introduction of human immunoglobulin (Ig) lociinto mice in which the endogenous Ig genes have been inactivated is onemeans of producing fully human monoclonal antibodies (mAbs) in mouse, ananimal that can be immunized with any desirable antigen. Using fullyhuman antibodies can minimize the immunogenic and allergic responsesthat can sometimes be caused by administering mouse or mouse-derivedmAbs to humans as therapeutic agents.

Fully human antibodies can be produced by immunizing transgenic animals(typically mice) that are capable of producing a repertoire of humanantibodies in the absence of endogenous immunoglobulin production.Antigens for this purpose typically have six or more contiguous aminoacids, and optionally are conjugated to a carrier, such as a hapten.See, e.g., Jakobovits et al., (1993) Proc. Natl. Acad. Sci. USA90:2551-2555; Jakobovits et al., (1993) Nature 362:255-258; andBruggermann et al., (1993) Year in Immunol. 7:33. In one example of sucha method, transgenic animals are produced by incapacitating theendogenous mouse immunoglobulin loci encoding the mouse heavy and lightimmunoglobulin chains therein, and inserting into the mouse genome largefragments of human genome DNA containing loci that encode human heavyand light chain proteins. Partially modified animals, which have lessthan the full complement of human immunoglobulin loci, are thencross-bred to obtain an animal having all of the desired immune systemmodifications. When administered an immunogen, these transgenic animalsproduce antibodies that are immunospecific for the immunogen but havehuman rather than murine amino acid sequences, including the variableregions. For further details of such methods, see, e.g., WO96/33735 andWO94/02602. Additional methods relating to transgenic mice for makinghuman antibodies are described in U.S. Pat. No. 5,545,807; U.S. Pat. No.6,713,610; U.S. Pat. No. 6,673,986; U.S. Pat. No. 6,162,963; U.S. Pat.No. 5,545,807; U.S. Pat. No. 6,300,129; U.S. Pat. No. 6,255,458; U.S.Pat. No. 5,877,397; U.S. Pat. No. 5,874,299 and U.S. Pat. No. 5,545,806;in PCT publications WO91/10741, WO90/04036, and in EP 546073 and EP546073.

According to certain embodiments, antibodies of the invention can beprepared through the utilization of a transgenic mouse that has asubstantial portion of the human antibody producing genome inserted butthat is rendered deficient in the production of endogenous, murineantibodies. Such mice, then, are capable of producing humanimmunoglobulin molecules and antibodies and are deficient in theproduction of murine immunoglobulin molecules and antibodies.Technologies utilized for achieving this result are disclosed in thepatents, applications and references disclosed in the specification,herein. In certain embodiments, one can employ methods such as thosedisclosed in PCT Published Application No. WO 98/24893 or in Mendez etal., (1997) Nature Genetics, 15:146-156, which are hereby incorporatedby reference for any purpose.

Generally, fully human monoclonal antibodies specific for a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR1c can be produced as follows. Transgenic mice containinghuman immunoglobulin genes are immunized with the antigen of interest,e.g. those described herein, lymphatic cells (such as B-cells) from themice that express antibodies are obtained. Such recovered cells arefused with a myeloid-type cell line to prepare immortal hybridoma celllines, and such hybridoma cell lines are screened and selected toidentify hybridoma cell lines that produce antibodies specific to theantigen of interest. In certain embodiments, the production of ahybridoma cell line that produces antibodies specific to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR1c is provided.

In certain embodiments, fully human antibodies can be produced byexposing human splenocytes (B or T cells) to an antigen in vitro, andthen reconstituting the exposed cells in an immunocompromised mouse,e.g. SCID or nod/SCID. See, e.g., Brams et al., J. Immunol. 160:2051-2058 (1998); Carballido et al., Nat. Med., 6: 103-106 (2000). Incertain such approaches, engraftment of human fetal tissue into SCIDmice (SCID-hu) results in long-term hematopoiesis and human T-celldevelopment. See, e.g., McCune et al., Science, 241:1532-1639 (1988);Ifversen et al., Sem. Immunol., 8:243-248 (1996). In certain instances,humoral immune response in such chimeric mice is dependent onco-development of human T-cells in the animals. See, e.g., Martensson etal., Immunol., 83:1271-179 (1994). In certain approaches, humanperipheral blood lymphocytes are transplanted into SCID mice. See, e.g.,Mosier et al., Nature, 335:256-259 (1988). In certain such embodiments,when such transplanted cells are treated either with a priming agent,such as Staphylococcal Enterotoxin A (SEA), or with anti-human CD40monoclonal antibodies, higher levels of B cell production is detected.See, e.g., Martensson et al., Immunol., 84: 224-230 (1995); Murphy etal., Blood, 86:1946-1953 (1995).

Thus, in certain embodiments, fully human antibodies can be produced bythe expression of recombinant DNA in host cells or by expression inhybridoma cells. In other embodiments, antibodies can be produced usingthe phage display techniques described herein.

The antibodies described herein were prepared through the utilization ofthe XENOMOUSE® technology, as described herein. Such mice, then, arecapable of producing human immunoglobulin molecules and antibodies andare deficient in the production of murine immunoglobulin molecules andantibodies. Technologies utilized for achieving the same are disclosedin the patents, applications, and references disclosed in the backgroundsection herein. In particular, however, a preferred embodiment oftransgenic production of mice and antibodies therefrom is disclosed inU.S. patent application Ser. No. 08/759,620, filed Dec. 3, 1996 andInternational Patent Application Nos. WO 98/24893, published Jun. 11,1998 and WO 00/76310, published Dec. 21, 2000, the disclosures of whichare hereby incorporated by reference. See also Mendez et al., NatureGenetics, 15:146-156 (1997), the disclosure of which is herebyincorporated by reference.

Through the use of such technology, fully human monoclonal antibodies toa variety of antigens have been produced. Essentially, XENOMOUSE® linesof mice are immunized with an antigen of interest (e.g. an antigenprovided herein), lymphatic cells (such as B-cells) are recovered fromthe hyper-immunized mice, and the recovered lymphocytes are fused with amyeloid-type cell line to prepare immortal hybridoma cell lines. Thesehybridoma cell lines are screened and selected to identify hybridomacell lines that produced antibodies specific to the antigen of interest.Provided herein are methods for the production of multiple hybridomacell lines that produce antibodies specific to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR1c.Further, provided herein are characterization of the antibodies producedby such cell lines, including nucleotide and amino acid sequenceanalyses of the heavy and light chains of such antibodies.

The production of the XENOMOUSE® strains of mice is further discussedand delineated in U.S. patent application Ser. No. 07/466,008, filedJan. 12, 1990, Ser. No. 07/610,515, filed Nov. 8, 1990, Ser. No.07/919,297, filed Jul. 24, 1992, Ser. No. 07/922,649, filed Jul. 30,1992, Ser. No. 08/031,801, filed Mar. 15, 1993, Ser. No. 08/112,848,filed Aug. 27, 1993, Ser. No. 08/234,145, filed Apr. 28, 1994, Ser. No.08/376,279, filed Jan. 20, 1995, 08/430,938, filed Apr. 27, 1995, Ser.No. 08/464,584, filed Jun. 5, 1995, Ser. No. 08/464,582, filed Jun. 5,1995, Ser. No. 08/463,191, filed Jun. 5, 1995, Ser. No. 08/462,837,filed Jun. 5, 1995, Ser. No. 08/486,853, filed Jun. 5, 1995, Ser. No.08/486,857, filed Jun. 5, 1995, Ser. No. 08/486,859, filed Jun. 5, 1995,Ser. No. 08/462,513, filed Jun. 5, 1995, Ser. No. 08/724,752, filed Oct.2, 1996, Ser. No. 08/759,620, filed Dec. 3, 1996, U.S. Publication2003/0093820, filed Nov. 30, 2001 and U.S. Pat. Nos. 6,162,963,6,150,584, 6,114,598, 6,075,181, and 5,939,598 and Japanese Patent Nos.3 068 180 B2, 3 068 506 B2, and 3 068 507 B2. See also European PatentNo., EP 0 463 151 B1, grant published Jun. 12, 1996, InternationalPatent Application No., WO 94/02602, published Feb. 3, 1994,International Patent Application No., WO 96/34096, published Oct. 31,1996, WO 98/24893, published Jun. 11, 1998, WO 00/76310, published Dec.21, 2000. The disclosures of each of the above-cited patents,applications, and references are hereby incorporated by reference intheir entirety.

Using hybridoma technology, antigen-specific human mAbs with the desiredspecificity can be produced and selected from the transgenic mice suchas those described herein. Such antibodies can be cloned and expressedusing a suitable vector and host cell, or the antibodies can beharvested from cultured hybridoma cells.

Fully human antibodies can also be derived from phage-display libraries(as described in Hoogenboom et al., (1991) J. Mol. Biol. 227:381; andMarks et al., (1991) J. Mol. Biol. 222:581). Phage display techniquesmimic immune selection through the display of antibody repertoires onthe surface of filamentous bacteriophage, and subsequent selection ofphage by their binding to an antigen of choice. One such technique isdescribed in PCT Publication No. WO 99/10494 (hereby incorporated byreference), which describes the isolation of high affinity andfunctional agonistic antibodies for MPL- and msk-receptors using such anapproach.

Bispecific or Bifunctional Antigen Binding Proteins

Also provided are bispecific and bifunctional antibodies that includeone or more CDRs or one or more variable regions as described above. Abispecific or bifunctional antibody in some instances can be anartificial hybrid antibody having two different heavy/light chain pairsand two different binding sites. Bispecific antibodies can be producedby a variety of methods including, but not limited to, fusion ofhybridomas or linking of Fab′ fragments. See, e.g., Songsivilai &Lachmann, (1990) Clin. Exp. Immunol. 79:315-321; Kostelny et al., (1992)J. Immunol. 148:1547-1553. When an antigen binding protein of theinstant disclosure binds to a complex comprising β-Klotho and at leastone of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, the binding may lead tothe activation of FGF21-like activity as measured by the FGF21-likefunctional and signaling assays described in Examples 4-6; when such anantigen binding protein is an antibody it is referred to as an agonisticantibody.

Various Other Forms

Some of the antigen binding proteins that specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c that are provided in the present disclosure include variantforms of the antigen binding proteins disclosed herein (e.g., thosehaving the sequences listed in Tables 1-4 and 6-23).

In various embodiments, the antigen binding proteins disclosed hereincan comprise one or more non-naturally occurring/encoded amino acids.For instance, some of the antigen binding proteins have one or morenon-naturally occurring/encoded amino acid substitutions in one or moreof the heavy or light chains, variable regions or CDRs listed in Tables1-23. Examples of non-naturally occurring/encoded amino acids (which canbe substituted for any naturally-occurring amino acid found in anysequence disclosed herein, as desired) include: 4-hydroxyproline,γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine,O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine,5-hydroxylysine, σ-N-methylarginine, and other similar amino acids andimino acids (e.g., 4-hydroxyproline). In the polypeptide notation usedherein, the left-hand direction is the amino terminal direction and theright-hand direction is the carboxyl-terminal direction, in accordancewith standard usage and convention. A non-limiting lists of examples ofnon-naturally occurring/encoded amino acids that can be inserted into anantigen binding protein sequence or substituted for a wild-type residuein an antigen binding sequence include β-amino acids, homoamino acids,cyclic amino acids and amino acids with derivatized side chains.Examples include (in the L-form or D-form; abbreviated as inparentheses): citrulline (Cit), homocitrulline (hCit),Nα-methylcitrulline (NMeCit), Nα-methylhomocitrulline (Nα-MeHoCit),ornithine (Orn), Nα-Methylornithine (Nα-MeOrn or NMeOrn), sarcosine(Sar), homolysine (hLys or hK), homoarginine (hArg or hR), homoglutamine(hQ), Nα-methylarginine (NMeR), Nα-methylleucine (Nα-MeL or NMeL),N-methylhomolysine (NMeHoK), Nα-methylglutamine (NMeQ), norleucine(Nle), norvaline (Nva), 1,2,3,4-tetrahydroisoquinoline (Tic),Octahydroindole-2-carboxylic acid (Oic), 3-(1-naphthy)alanine (1-Nal),3-(2-naphthyl)alanine (2-Nal), 1,2,3,4-tetrahydroisoquinoline (Tic),2-indanylglycine (IgI), para-iodophenylalanine (pI-Phe),para-aminophenylalanine (4AmP or 4-Amino-Phe), 4-guanidino phenylalanine(Guf), glycyllysine (abbreviated “K(Nε-glycyl)” or “K(glycyl)” or“K(gly)”), nitrophenylalanine (nitrophe), aminophenylalanine (aminopheor Amino-Phe), benzylphenylalanine (benzylphe), γ-carboxyglutamic acid(γ-carboxyglu), hydroxyproline (hydroxypro), p-carboxyl-phenylalanine(Cpa), α-aminoadipic acid (Aad), Nα-methyl valine (NMeVal), N-α-methylleucine (NMeLeu), Nα-methylnorleucine (NMeNle), cyclopentylglycine(Cpg), cyclohexylglycine (Chg), acetylarginine (acetylarg), α,β-diaminopropionoic acid (Dpr), α, γ-diaminobutyric acid (Dab),diaminopropionic acid (Dap), cyclohexylalanine (Cha),4-methyl-phenylalanine (MePhe), β, β-diphenyl-alanine (BiPhA),aminobutyric acid (Abu), 4-phenyl-phenylalanine (or biphenylalanine;4Bip), α-amino-isobutyric acid (Aib), beta-alanine, beta-aminopropionicacid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid,aminopimelic acid, desmosine, diaminopimelic acid, N-ethylglycine,N-ethylaspargine, hydroxylysine, allo-hydroxylysine, isodesmosine,allo-isoleucine, N-methylglycine, N-methylisoleucine, N-methylvaline,4-hydroxyproline (Hyp), γ-carboxyglutamate, ε-N,N,N-trimethyllysine,ε-N-acetyllysine, 0-phosphoserine, N-acetylserine, N-formylmethionine,3-methylhistidine, 5-hydroxylysine, ω-methylarginine, 4-Amino-O-PhthalicAcid (4APA), and other similar amino acids, and derivatized forms of anyof those specifically listed.

Additionally, the antigen binding proteins can have one or moreconservative amino acid substitutions in one or more of the heavy orlight chains, variable regions or CDRs listed in Tables 1-4 and 6-23.Naturally-occurring amino acids can be divided into classes based oncommon side chain properties:

1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile;

2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;

3) acidic: Asp, Glu;

4) basic: His, Lys, Arg;

5) residues that influence chain orientation: Gly, Pro; and

6) aromatic: Trp, Tyr, Phe.

Conservative amino acid substitutions can involve exchange of a memberof one of these classes with another member of the same class.Conservative amino acid substitutions can encompass non-naturallyoccurring/encoded amino acid residues, which are typically incorporatedby chemical peptide synthesis rather than by synthesis in biologicalsystems. See Table 8, infra. These include peptidomimetics and otherreversed or inverted forms of amino acid moieties.

Non-conservative substitutions can involve the exchange of a member ofone of the above classes for a member from another class. Suchsubstituted residues can be introduced into regions of the antibody thatare homologous with human antibodies, or into the non-homologous regionsof the molecule.

In making such changes, according to certain embodiments, thehydropathic index of amino acids can be considered. The hydropathicprofile of a protein is calculated by assigning each amino acid anumerical value (“hydropathy index”) and then repetitively averagingthese values along the peptide chain. Each amino acid has been assigneda hydropathic index on the basis of its hydrophobicity and chargecharacteristics. They are: isoleucine (+4.5); valine (+4.2); leucine(+3.8); phenylalanine (+2.8); cysteine/cystine (+2.5); methionine(+1.9); alanine (+1.8); glycine (−0.4); threonine (−0.7); serine (−0.8);tryptophan (−0.9); tyrosine (−1.3); proline (−1.6); histidine (−3.2);glutamate (−3.5); glutamine (−3.5); aspartate (−3.5); asparagine (−3.5);lysine (−3.9); and arginine (−4.5).

The importance of the hydropathic profile in conferring interactivebiological function on a protein is understood in the art (see, e.g.,Kyte et al., 1982, J. Mol. Biol. 157:105-131). It is known that certainamino acids can be substituted for other amino acids having a similarhydropathic index or score and still retain a similar biologicalactivity. In making changes based upon the hydropathic index, in certainembodiments, the substitution of amino acids whose hydropathic indicesare within ±2 is included. In some aspects, those which are within ±1are included, and in other aspects, those within ±0.5 are included.

It is also understood in the art that the substitution of like aminoacids can be made effectively on the basis of hydrophilicity,particularly where the biologically functional protein or peptidethereby created is intended for use in immunological embodiments, as inthe present case. In certain embodiments, the greatest local averagehydrophilicity of a protein, as governed by the hydrophilicity of itsadjacent amino acids, correlates with its immunogenicity andantigen-binding or immunogenicity, that is, with a biological propertyof the protein.

The following hydrophilicity values have been assigned to these aminoacid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0±1);glutamate (+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2);glycine (0); threonine (−0.4); proline (−0.5±1); alanine (−0.5);histidine (−0.5); cysteine (−1.0); methionine (−1.3); valine (−1.5);leucine (−1.8); isoleucine (−1.8); tyrosine (−2.3); phenylalanine (−2.5)and tryptophan (−3.4). In making changes based upon similarhydrophilicity values, in certain embodiments, the substitution of aminoacids whose hydrophilicity values are within ±2 is included, in otherembodiments, those which are within ±1 are included, and in still otherembodiments, those within ±0.5 are included. In some instances, one canalso identify epitopes from primary amino acid sequences on the basis ofhydrophilicity. These regions are also referred to as “epitopic coreregions.”

Exemplary conservative amino acid substitutions are set forth in Table8.

TABLE 8 Conservative Amino Acid Substitutions Original Residue ExemplarySubstitutions Ala Ser Arg Lys Asn Gln, His Asp Glu Cys Ser Gln Asn GluAsp Gly Pro His Asn, Gln Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu MetLeu, Ile Phe Met, Leu, Tyr Ser Thr Thr Ser Trp Tyr Tyr Trp, Phe Val Ile,Leu

A skilled artisan will be able to determine suitable variants ofpolypeptides as set forth herein using well-known techniques coupledwith the information provided herein. One skilled in the art canidentify suitable areas of the molecule that can be changed withoutdestroying activity by targeting regions not believed to be importantfor activity. The skilled artisan also will be able to identify residuesand portions of the molecules that are conserved among similarpolypeptides. In further embodiments, even areas that can be importantfor biological activity or for structure can be subject to conservativeamino acid substitutions without destroying the biological activity orwithout adversely affecting the polypeptide structure.

Additionally, one skilled in the art can review structure-functionstudies identifying residues in similar polypeptides that are importantfor activity or structure. In view of such a comparison, one can predictthe importance of amino acid residues in a protein that correspond toamino acid residues important for activity or structure in similarproteins. One skilled in the art can opt for chemically similar aminoacid substitutions for such predicted important amino acid residues.

One skilled in the art can also analyze the three-dimensional structureand amino acid sequence in relation to that structure in similarpolypeptides. In view of such information, one skilled in the art canpredict the alignment of amino acid residues of an antibody with respectto its three dimensional structure. One skilled in the art can choosenot to make radical changes to amino acid residues predicted to be onthe surface of the protein, since such residues can be involved inimportant interactions with other molecules. Moreover, one skilled inthe art can generate test variants containing a single amino acidsubstitution at each desired amino acid residue. These variants can thenbe screened using assays for FGF21-like signaling, (including thosedescribed in the Examples provided herein) thus yielding informationregarding which amino acids can be changed and which must not bechanged. In other words, based on information gathered from such routineexperiments, one skilled in the art can readily determine the amino acidpositions where further substitutions should be avoided either alone orin combination with other mutations.

A number of scientific publications have been devoted to the predictionof secondary structure. See, Moult, (1996) Curr. Op. in Biotech.7:422-427; Chou et al., (1974) Biochem. 13:222-245; Chou et al., (1974)Biochemistry 113:211-222; Chou et al., (1978) Adv. Enzymol. Relat AreasMol. Biol. 47:45-148; Chou et al., (1979) Ann. Rev. Biochem. 47:251-276;and Chou et al., (1979) Biophys. J. 26:367-384. Moreover, computerprograms are currently available to assist with predicting secondarystructure. One method of predicting secondary structure is based uponhomology modeling. For example, two polypeptides or proteins that have asequence identity of greater than 30%, or similarity greater than 40%can have similar structural topologies. The growth of the proteinstructural database (PDB) has provided enhanced predictability ofsecondary structure, including the potential number of folds within apolypeptide's or protein's structure. See, Holm et al., (1999) Nucl.Acid. Res. 27:244-247. It has been suggested (Brenner et al., (1997)Curr. Op. Struct. Biol. 7:369-376) that there are a limited number offolds in a given polypeptide or protein and that once a critical numberof structures have been resolved, structural prediction will becomedramatically more accurate.

Additional methods of predicting secondary structure include “threading”(Jones, (1997) Curr. Opin. Struct. Biol. 7:377-387; Sippl et al., (1996)Structure 4:15-19), “profile analysis” (Bowie et al., (1991) Science253:164-170; Gribskov et al., (1990) Meth. Enzym. 183:146-159; Gribskovet al., (1987) Proc. Nat. Acad. Sci. 84:4355-4358), and “evolutionarylinkage” (See, Holm, (1999) supra; and Brenner, (1997) supra).

In some embodiments, amino acid substitutions are made that: (1) reducesusceptibility to proteolysis, (2) reduce susceptibility to oxidation,(3) alter binding affinity for forming protein complexes, (4) alterligand or antigen binding affinities, and/or (4) confer or modify otherphysicochemical or functional properties on such polypeptides. Forexample, single or multiple amino acid substitutions (in someembodiments, conservative amino acid substitutions) can be made in thenaturally-occurring sequence. Substitutions can be made in that portionof the antibody that lies outside the domain(s) forming intermolecularcontacts. In such embodiments, conservative amino acid substitutions canbe used that do not substantially change the structural characteristicsof the parent sequence (e.g., one or more replacement amino acids thatdo not disrupt the secondary structure that characterizes the parent ornative antigen binding protein). Examples of art-recognized polypeptidesecondary and tertiary structures are described in Creighton, Proteins:Structures and Molecular Properties 2nd edition, 1992, W. H. Freeman &Company; Creighton, Proteins: Structures and Molecular Principles, 1984,W. H. Freeman & Company; Introduction to Protein Structure (Branden andTooze, eds.), 2nd edition, 1999, Garland Publishing; Petsko & Ringe,Protein Structure and Function, 2004, New Science Press Ltd; andThornton et al., (1991) Nature 354:105, which are each incorporatedherein by reference.

Additional preferred antibody variants include cysteine variants whereinone or more cysteine residues in the parent or native amino acidsequence are deleted from or substituted with another amino acid (e.g.,serine). Cysteine variants are useful, inter alia when antibodies mustbe refolded into a biologically active conformation. Cysteine variantscan have fewer cysteine residues than the native antibody, and typicallyhave an even number to minimize interactions resulting from unpairedcysteines.

The heavy and light chains, variable regions domains and CDRs that aredisclosed can be used to prepare polypeptides that contain an antigenbinding region that can specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cand may induce FGF21-like signaling. For example, one or more of theCDRs listed in Tables 3-4 and 21-23 can be incorporated into a molecule(e.g., a polypeptide) covalently or noncovalently to make animmunoadhesion. An immunoadhesion can incorporate the CDR(s) as part ofa larger polypeptide chain, can covalently link the CDR(s) to anotherpolypeptide chain, or can incorporate the CDR(s) noncovalently. TheCDR(s) enable the immunoadhesion to bind specifically to a particularantigen of interest (e.g., to a complex comprising β-Klotho and at leastone of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c or an epitope thereon).

The heavy and light chains, variable regions domains and CDRs that aredisclosed can be used to prepare polypeptides that contain an antigenbinding region that can specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cand may induce FGF21-like signaling. For example, one or more of theCDRs listed in Tables 3-4 and 21-23 can be incorporated into a molecule(e.g., a polypeptide) that is structurally similar to a “half” antibodycomprising the heavy chain, the light chain of an antigen bindingprotein paired with a Fc fragment so that the antigen binding region ismonovalent (like a Fab fragment) but with a dimeric Fc moiety.

Mimetics (e.g., “peptide mimetics” or “peptidomimetics”) based upon thevariable region domains and CDRs that are described herein are alsoprovided. These analogs can be peptides, non-peptides or combinations ofpeptide and non-peptide regions. Fauchere, (1986) Adv. Drug Res. 15:29;Veber and Freidinger, (1985) TINS p. 392; and Evans et al., (1987) J.Med. Chem. 30:1229, which are incorporated herein by reference for anypurpose. Peptide mimetics that are structurally similar totherapeutically useful peptides can be used to produce a similartherapeutic or prophylactic effect. Such compounds are often developedwith the aid of computerized molecular modeling. Generally,peptidomimetics are proteins that are structurally similar to anantibody displaying a desired biological activity, such as here theability to specifically bind to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, but have one ormore peptide linkages optionally replaced by a linkage selected from:—CH₂NH—, —CH₂S—, —CH₂—CH₂—, —CH—CH-(cis and trans), —COCH₂—,—CH(OH)CH₂—, and —CH₂SO—, by methods well known in the art. Systematicsubstitution of one or more amino acids of a consensus sequence with aD-amino acid of the same type (e.g., D-lysine in place of L-lysine) canbe used in certain embodiments to generate more stable proteins. Inaddition, constrained peptides comprising a consensus sequence or asubstantially identical consensus sequence variation can be generated bymethods known in the art (Rizo and Gierasch, (1992) Ann. Rev. Biochem.61:387), incorporated herein by reference), for example, by addinginternal cysteine residues capable of forming intramolecular disulfidebridges which cyclize the peptide.

Derivatives of the antigen binding proteins that specifically bind to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c that are described herein are also provided. Thederivatized antigen binding proteins can comprise any molecule orsubstance that imparts a desired property to the antibody or fragment,such as increased half-life in a particular use. The derivatized antigenbinding protein can comprise, for example, a detectable (or labeling)moiety (e.g., a radioactive, colorimetric, antigenic or enzymaticmolecule, a detectable bead (such as a magnetic or electrodense (e.g.,gold) bead), or a molecule that binds to another molecule (e.g., biotinor streptavidin), a therapeutic or diagnostic moiety (e.g., aradioactive, cytotoxic, or pharmaceutically active moiety), or amolecule that increases the suitability of the antigen binding proteinfor a particular use (e.g., administration to a subject, such as a humansubject, or other in vivo or in vitro uses). Examples of molecules thatcan be used to derivatize an antigen binding protein include albumin(e.g., human serum albumin) and polyethylene glycol (PEG).Albumin-linked and PEGylated derivatives of antigen binding proteins canbe prepared using techniques well known in the art. Certain antigenbinding proteins include a PEGylated single chain polypeptide asdescribed herein. In one embodiment, the antigen binding protein isconjugated or otherwise linked to transthyretin (“TTR”) or a TTRvariant. The TTR or TTR variant can be chemically modified with, forexample, a chemical selected from the group consisting of dextran,poly(n-vinyl pyrrolidone), polyethylene glycols, propropylene glycolhomopolymers, polypropylene oxide/ethylene oxide co-polymers,polyoxyethylated polyols and polyvinyl alcohols.

Other derivatives include covalent or aggregative conjugates of theantigen binding proteins that specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cthat are disclosed herein with other proteins or polypeptides, such asby expression of recombinant fusion proteins comprising heterologouspolypeptides fused to the N-terminus or C-terminus of an antigen bindingprotein that induces FGF21-like signaling. For example, the conjugatedpeptide can be a heterologous signal (or leader) polypeptide, e.g., theyeast alpha-factor leader, or a peptide such as an epitope tag. Anantigen binding protein-containing fusion protein of the presentdisclosure can comprise peptides added to facilitate purification oridentification of an antigen binding protein that specifically binds toa complex comprising β-Klotho and at least one of (i) FGFR1c, (ii)FGFR2c and (iii) FGFR3c (e.g., a poly-His tag) and that can induceFGF21-like signaling. An antigen binding protein that specifically bindsto a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii)FGFR2c and (iii) FGFR3c also can be linked to the FLAG peptide asdescribed in Hopp et al., (1988) Bio/Technology 6:1204; and U.S. Pat.No. 5,011,912. The FLAG peptide is highly antigenic and provides anepitope reversibly bound by a specific monoclonal antibody (mAb),enabling rapid assay and facile purification of expressed recombinantprotein. Reagents useful for preparing fusion proteins in which the FLAGpeptide is fused to a given polypeptide are commercially available(Sigma, St. Louis, Mo.).

Multimers that comprise one or more antigen binding proteins thatspecifically bind to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c form another aspect of thepresent disclosure. Multimers can take the form of covalently-linked ornon-covalently-linked dimers, trimers, or higher multimers. Multimerscomprising two or more antigen binding proteins that bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c and which may induce FGF21-like signaling are contemplatedfor use as therapeutics, diagnostics and for other uses as well, withone example of such a multimer being a homodimer. Other exemplarymultimers include heterodimers, homotrimers, heterotrimers,homotetramers, heterotetramers, etc.

One embodiment is directed to multimers comprising multiple antigenbinding proteins that specifically bind to a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c joined viacovalent or non-covalent interactions between peptide moieties fused toan antigen binding protein that specifically binds to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c. Such peptides can be peptide linkers (spacers), orpeptides that have the property of promoting multimerization. Leucinezippers and certain polypeptides derived from antibodies are among thepeptides that can promote multimerization of antigen binding proteinsattached thereto, as described in more detail herein.

In particular embodiments, the multimers comprise from two to fourantigen binding proteins that bind to a complex comprising β-Klotho andat least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. The antigenbinding protein moieties of the multimer can be in any of the formsdescribed above, e.g., variants or fragments. Preferably, the multimerscomprise antigen binding proteins that have the ability to specificallybind to a complex comprising β-Klotho and at least one of (i) FGFR1c,(ii) FGFR2c and (iii) FGFR3c.

In one embodiment, an oligomer is prepared using polypeptides derivedfrom immunoglobulins. Preparation of fusion proteins comprising certainheterologous polypeptides fused to various portions of antibody-derivedpolypeptides (including the Fc domain) has been described, e.g., byAshkenazi et al., (1991) Proc. Natl. Acad. Sci. USA 88:10535; Byrn etal., (1990) Nature 344:677; and Hollenbaugh et al., (1992) CurrentProtocols in Immunology, Suppl. 4, pages 10.19.1-10.19.11.

One embodiment comprises a dimer comprising two fusion proteins createdby fusing an antigen binding protein that specifically binds to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c to the Fc region of an antibody. The dimer can be madeby, for example, inserting a gene fusion encoding the fusion proteininto an appropriate expression vector, expressing the gene fusion inhost cells transformed with the recombinant expression vector, andallowing the expressed fusion protein to assemble much like antibodymolecules, whereupon interchain disulfide bonds form between the Fcmoieties to yield the dimer.

The term “Fc polypeptide” as used herein includes native and muteinforms of polypeptides derived from the Fc region of an antibody.Truncated forms of such polypeptides containing the hinge region thatpromotes dimerization also are included. Fusion proteins comprising Fcmoieties (and oligomers formed therefrom) offer the advantage of facilepurification by affinity chromatography over Protein A or Protein Gcolumns.

One suitable Fc polypeptide, described in PCT application WO 93/10151and U.S. Pat. No. 5,426,048 and U.S. Pat. No. 5,262,522, is a singlechain polypeptide extending from the N-terminal hinge region to thenative C-terminus of the Fc region of a human IgG1 antibody. Anotheruseful Fc polypeptide is the Fc mutein described in U.S. Pat. No.5,457,035, and in Baum et al., (1994) EMBO J. 13:3992-4001. The aminoacid sequence of this mutein is identical to that of the native Fcsequence presented in WO 93/10151, except that amino acid 19 has beenchanged from Leu to Ala, amino acid 20 has been changed from Leu to Glu,and amino acid 22 has been changed from Gly to Ala. The mutein exhibitsreduced affinity for Fc receptors.

In other embodiments, the variable portion of the heavy and/or lightchains of a antigen binding protein such as disclosed herein can besubstituted for the variable portion of an antibody heavy and/or lightchain.

Alternatively, the oligomer is a fusion protein comprising multipleantigen binding proteins that specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cwith or without peptide linkers (spacer peptides). Among the suitablepeptide linkers are those described in U.S. Pat. No. 4,751,180 and U.S.Pat. No. 4,935,233.

Another method for preparing oligomeric derivatives comprising thatantigen binding proteins that specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cinvolves use of a leucine zipper. Leucine zipper domains are peptidesthat promote oligomerization of the proteins in which they are found.Leucine zippers were originally identified in several DNA-bindingproteins (Landschultz et al., (1988) Science 240:1759-64), and havesince been found in a variety of different proteins. Among the knownleucine zippers are naturally occurring peptides and derivatives thereofthat dimerize or trimerize. Examples of leucine zipper domains suitablefor producing soluble oligomeric proteins are described in PCTapplication WO 94/10308, and the leucine zipper derived from lungsurfactant protein D (SPD) described in Hoppe et al., (1994) FEBSLetters 344:191, hereby incorporated by reference. The use of a modifiedleucine zipper that allows for stable trimerization of a heterologousprotein fused thereto is described in Fanslow et al., (1994) Semin.Immunol. 6:267-278. In one approach, recombinant fusion proteinscomprising an antigen binding protein fragment or derivative thatspecifically binds to a complex comprising β-Klotho and an FGFR (e.g.,FGFR1c, FGFR2c or FGFR3c) is fused to a leucine zipper peptide areexpressed in suitable host cells, and the soluble oligomeric antigenbinding protein fragments or derivatives that form are recovered fromthe culture supernatant.

In certain embodiments, the antigen binding protein has a K_(D)(equilibrium binding affinity) of less than 1 pM, 10 pM, 100 pM, 1 nM, 2nM, 5 nM, 10 nM, 25 nM or 50 nM.

In another aspect the instant disclosure provides an antigen bindingprotein having a half-life of at least one day in vitro or in vivo(e.g., when administered to a human subject). In one embodiment, theantigen binding protein has a half-life of at least three days. Inanother embodiment, the antibody or portion thereof has a half-life offour days or longer. In another embodiment, the antibody or portionthereof has a half-life of eight days or longer. In another embodiment,the antibody or portion thereof has a half-life of ten days or longer.In another embodiment, the antibody or portion thereof has a half-lifeof eleven days or longer. In another embodiment, the antibody or portionthereof has a half-life of fifteen days or longer. In anotherembodiment, the antibody or antigen-binding portion thereof isderivatized or modified such that it has a longer half-life as comparedto the underivatized or unmodified antibody. In another embodiment, anantigen binding protein that specifically binds to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3ccontains point mutations to increase serum half life, such as describedin WO 00/09560, published Feb. 24, 2000, incorporated by reference.

Glycosylation

An antigen binding protein that specifically binds to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c can have a glycosylation pattern that is different oraltered from that found in the native species. As is known in the art,glycosylation patterns can depend on both the sequence of the protein(e.g., the presence or absence of particular glycosylation amino acidresidues, discussed below), or the host cell or organism in which theprotein is produced. Particular expression systems are discussed below.

Glycosylation of polypeptides is typically either N-linked or O-linked.N-linked refers to the attachment of the carbohydrate moiety to the sidechain of an asparagine residue. The tri-peptide sequencesasparagine-X-serine and asparagine-X-threonine, where X is any aminoacid except proline, are the recognition sequences for enzymaticattachment of the carbohydrate moiety to the asparagine side chain.Thus, the presence of either of these tri-peptide sequences in apolypeptide creates a potential glycosylation site. O-linkedglycosylation refers to the attachment of one of the sugarsN-acetylgalactosamine, galactose, or xylose, to a hydroxyamino acid,most commonly serine or threonine, although 5-hydroxyproline or5-hydroxylysine can also be used.

Addition of glycosylation sites to the antigen binding protein isconveniently accomplished by altering the amino acid sequence such thatit contains one or more of the above-described tri-peptide sequences(for N-linked glycosylation sites). The alteration can also be made bythe addition of, or substitution by, one or more serine or threonineresidues to the starting sequence (for O-linked glycosylation sites).For ease, the antigen binding protein amino acid sequence can be alteredthrough changes at the DNA level, particularly by mutating the DNAencoding the target polypeptide at preselected bases such that codonsare generated that will translate into the desired amino acids.

Another means of increasing the number of carbohydrate moieties on theantigen binding protein is by chemical or enzymatic coupling ofglycosides to the protein. These procedures are advantageous in thatthey do not require production of the protein in a host cell that hasglycosylation capabilities for N- and O-linked glycosylation. Dependingon the coupling mode used, the sugar(s) can be attached to (a) arginineand histidine; (b) free carboxyl groups; (c) free sulfhydryl groups suchas those of cysteine; (d) free hydroxyl groups such as those of serine,threonine, or hydroxyproline; (e) aromatic residues such as those ofphenylalanine, tyrosine, or tryptophan; or (0 the amide group ofglutamine. These methods are described in WO 87/05330 and in Aplin &Wriston, (1981) CRC Crit. Rev. Biochem. 10:259-306.

Removal of carbohydrate moieties present on the starting antigen bindingprotein can be accomplished chemically or enzymatically. Chemicaldeglycosylation requires exposure of the protein to the compoundtrifluoromethanesulfonic acid, or an equivalent compound. This treatmentresults in the cleavage of most or all sugars except the linking sugar(N-acetylglucosamine or N-acetylgalactosamine), while leaving thepolypeptide intact. Chemical deglycosylation is described by Hakimuddinet al., (1987) Arch. Biochem. Biophys. 259:52-57 and by Edge et al.,(1981) Anal. Biochem. 118:131-37. Enzymatic cleavage of carbohydratemoieties on polypeptides can be achieved by the use of a variety ofendo- and exo-glycosidases as described by Thotakura et al., (1987)Meth. Enzymol. 138:350-59. Glycosylation at potential glycosylationsites can be prevented by the use of the compound tunicamycin asdescribed by Duskin et al., (1982) J. Biol. Chem. 257:3105-09.Tunicamycin blocks the formation of protein-N-glycoside linkages.

Hence, aspects of the present disclosure include glycosylation variantsof antigen binding proteins that specifically bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c wherein the number and/or type of glycosylation site(s) hasbeen altered compared to the amino acid sequences of the parentpolypeptide. In certain embodiments, antibody protein variants comprisea greater or a lesser number of N-linked glycosylation sites than thenative antibody. An N-linked glycosylation site is characterized by thesequence: Asn-X-Ser or Asn-X-Thr, wherein the amino acid residuedesignated as X can be any amino acid residue except proline. Thesubstitution of amino acid residues to create this sequence provides apotential new site for the addition of an N-linked carbohydrate chain.Alternatively, substitutions that eliminate or alter this sequence willprevent addition of an N-linked carbohydrate chain present in the nativepolypeptide. For example, the glycosylation can be reduced by thedeletion of an Asn or by substituting the Asn with a different aminoacid. In other embodiments, one or more new N-linked sites are created.Antibodies typically have a N-linked glycosylation site in the Fcregion.

Labels and Effector Groups

In some embodiments, an antigen binding protein that specifically bindsto a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii)FGFR2c and (iii) FGFR3c comprises one or more labels. The term “labelinggroup” or “label” means any detectable label. Examples of suitablelabeling groups include, but are not limited to, the following:radioisotopes or radionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc,¹¹¹In, ¹²⁵I, ¹³¹I) fluorescent groups (e.g., FITC, rhodamine, lanthanidephosphors), enzymatic groups (e.g., horseradish peroxidase,β-galactosidase, luciferase, alkaline phosphatase), chemiluminescentgroups, biotinyl groups, or predetermined polypeptide epitopesrecognized by a secondary reporter (e.g., leucine zipper pair sequences,binding sites for secondary antibodies, metal binding domains, epitopetags). In some embodiments, the labeling group is coupled to the antigenbinding protein via spacer arms of various lengths to reduce potentialsteric hindrance. Various methods for labeling proteins are known in theart and can be used as is seen fit.

The term “effector group” means any group coupled to an antigen bindingprotein that specifically binds to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and that acts as acytotoxic agent. Examples for suitable effector groups are radioisotopesor radionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I)Other suitable groups include toxins, therapeutic groups, orchemotherapeutic groups. Examples of suitable groups includecalicheamicin, auristatins, geldanamycin and cantansine. In someembodiments, the effector group is coupled to the antigen bindingprotein via spacer arms of various lengths to reduce potential sterichindrance.

In general, labels fall into a variety of classes, depending on theassay in which they are to be detected: a) isotopic labels, which can beradioactive or heavy isotopes; b) magnetic labels (e.g., magneticparticles); c) redox active moieties; d) optical dyes; enzymatic groups(e.g. horseradish peroxidase, β-galactosidase, luciferase, alkalinephosphatase); e) biotinylated groups; and f) predetermined polypeptideepitopes recognized by a secondary reporter (e.g., leucine zipper pairsequences, binding sites for secondary antibodies, metal bindingdomains, epitope tags, etc.). In some embodiments, the labeling group iscoupled to the antigen binding protein via spacer arms of variouslengths to reduce potential steric hindrance. Various methods forlabeling proteins are known in the art.

Specific labels include optical dyes, including, but not limited to,chromophores, phosphors and fluorophores, with the latter being specificin many instances. Fluorophores can be either “small molecule” fluores,or proteinaceous fluores.

By “fluorescent label” is meant any molecule that can be detected viaits inherent fluorescent properties. Suitable fluorescent labelsinclude, but are not limited to, fluorescein, rhodamine,tetramethylrhodamine, eosin, erythrosin, coumarin, methyl-coumarins,pyrene, Malacite green, stilbene, Lucifer Yellow, Cascade Blue, TexasRed, IAEDANS, EDANS, BODIPY FL, LC Red 640, Cy 5, Cy 5.5, LC Red 705,Oregon green, the Alexa-Fluor dyes (Alexa Fluor 350, Alexa Fluor 430,Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594,Alexa Fluor 633, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680),Cascade Blue, Cascade Yellow and R-phycoerythrin (PE) (Molecular Probes,Eugene, Oreg.), FITC, Rhodamine, and Texas Red (Pierce, Rockford, Ill.),CyS, Cy5.5, Cy7 (Amersham Life Science, Pittsburgh, Pa.). Suitableoptical dyes, including fluorophores, are described in Molecular ProbesHandbook by Richard P. Haugland and in subsequent editions, includingMolecular Probes Handbook, A Guide to Fluorescent Probes and LabelingTechnologies, 11^(th) edition, Johnson and Spence (eds), herebyexpressly incorporated by reference.

Suitable proteinaceous fluorescent labels also include, but are notlimited to, green fluorescent protein, including a Renilla, Ptilosarcus,or Aequorea species of GFP (Chalfie et al., (1994) Science 263:802-805),eGFP (Clontech Labs., Inc., Genbank Accession Number U55762), bluefluorescent protein (BFP, Quantum Biotechnologies, Inc., Quebec, Canada;Stauber, (1998) Biotechniques 24:462-71; Heim et al., (1996) Curr. Biol.6:178-82), enhanced yellow fluorescent protein (EYFP, Clontech Labs.,Inc.), luciferase (Ichiki et al., (1993) J. Immunol. 150:5408-17),β-galactosidase (Nolan et al., (1988) Proc. Natl. Acad. Sci. U.S.A.85:2603-07) and Renilla (WO92/15673, WO95/07463, WO98/14605, WO98/26277,WO99/49019, U.S. Pat. Nos. 5,292,658, 5,418,155, 5,683,888, 5,741,668,5,777,079, 5,804,387, 5,874,304, 5,876,995 and 5,925,558).

Preparing of Antigen Binding Proteins

Non-human antibodies that are provided can be, for example, derived fromany antibody-producing animal, such as a mouse, rat, rabbit, goat,donkey, or non-human primate (such as a monkey, (e.g., cynomolgus orrhesus monkey) or an ape (e.g., chimpanzee)). Non-human antibodies canbe used, for instance, in in vitro cell culture and cell-culture basedapplications, or any other application where an immune response to theantibody does not occur or is insignificant, can be prevented, is not aconcern, or is desired. In certain embodiments, the antibodies can beproduced by immunizing with cell bound receptor from CHO transfectantsexpressing full length human FGFR1c and β-Klotho at the cell surfacefollowing incubated with FGF21; or with cell bound receptor of 293Ttransfectants expressing full length human β-Klotho and an N-terminaltruncated version of human FGFR1c encompassing amino acid residues 141to 822 of the polypeptide of SEQ ID NO: 4; or with full-length β-Klotho,FGFR1c, FGFR2c or FGFR3c; or with the extracellular domain of β-Klotho,FGFR1c, FGFR2c or FGFR3c; or with two of β-Klotho, FGFR1c, FGFR2c, andFGFR3c; or with whole cells expressing FGFR1c, β-Klotho or both FGFR1cand β-Klotho; or with membranes prepared from cells expressing FGFR1c,β-Klotho or both FGFR1c and β-Klotho; or with fusion proteins, e.g., Fcfusions comprising FGFR1c, β-Klotho or FGFR1c and β-Klotho (orextracellular domains thereof) fused to Fc, and other methods known inthe art, e.g., as described in the Examples presented herein.Alternatively, the certain non-human antibodies can be raised byimmunizing with amino acids which are segments of one or more ofβ-Klotho, FGFR1c, FGFR2c or FGFR3c that form part of the epitope towhich certain antibodies provided herein bind. The antibodies can bepolyclonal, monoclonal, or can be synthesized in host cells byexpressing recombinant DNA.

Fully human antibodies can be prepared as described above by immunizingtransgenic animals containing human immunoglobulin loci or by selectinga phage display library that is expressing a repertoire of humanantibodies.

The monoclonal antibodies (mAbs) can be produced by a variety oftechniques, including conventional monoclonal antibody methodology,e.g., the standard somatic cell hybridization technique of Kohler &Milstein, (1975) Nature 256:495-97. Alternatively, other techniques forproducing monoclonal antibodies can be employed, for example, the viralor oncogenic transformation of B-lymphocytes. One suitable animal systemfor preparing hybridomas is the murine system, which is a very wellestablished procedure. Immunization protocols and techniques forisolation of immunized splenocytes for fusion are known in the art. Forsuch procedures, B cells from immunized mice are fused with a suitableimmortalized fusion partner, such as a murine myeloma cell line. Ifdesired, rats or other mammals besides can be immunized instead of miceand B cells from such animals can be fused with the murine myeloma cellline to form hybridomas. Alternatively, a myeloma cell line from asource other than mouse can be used. Fusion procedures for makinghybridomas also are well known. SLAM technology can also be employed inthe production of antibodies.

The single chain antibodies that are provided can be formed by linkingheavy and light chain variable domain (Fv region) fragments via an aminoacid bridge (short peptide linker), resulting in a single polypeptidechain. Such single-chain Fvs (scFvs) can be prepared by fusing DNAencoding a peptide linker between DNAs encoding the two variable domainpolypeptides (V_(L) and V_(H)). The resulting polypeptides can fold backon themselves to form antigen-binding monomers, or they can formmultimers (e.g., dimers, trimers, or tetramers), depending on the lengthof a flexible linker between the two variable domains (Kortt et al.,(1997) Prot. Eng. 10:423; Kortt et al., (2001) Biomol. Eng. 18:95-108).By combining different V_(L) and V_(H)-comprising polypeptides, one canform multimeric scFvs that bind to different epitopes (Kriangkum et al.,(2001) Biomol. Eng. 18:31-40). Techniques developed for the productionof single chain antibodies include those described in U.S. Pat. No.4,946,778; Bird et al., (1988) Science 242:423-26; Huston et al., (1988)Proc. Natl. Acad. Sci. U.S.A. 85:5879-83; Ward et al., (1989) Nature334:544-46, de Graaf et al., (2002)Methods Mol Biol. 178:379-387. Singlechain antibodies derived from antibodies provided herein include, butare not limited to scFvs comprising the variable domain combinations ofthe heavy and light chain variable regions depicted in Table 2, orcombinations of light and heavy chain variable domains which include theCDRs depicted in Tables 3-4 and 6-23.

Antibodies provided herein that are of one subclass can be changed toantibodies from a different subclass using subclass switching methods.Thus, IgG antibodies can be derived from an IgM antibody, for example,and vice versa. Such techniques allow the preparation of new antibodiesthat possess the antigen binding properties of a given antibody (theparent antibody), but also exhibit biological properties associated withan antibody isotype or subclass different from that of the parentantibody. Recombinant DNA techniques can be employed. Cloned DNAencoding particular antibody polypeptides can be employed in suchprocedures, e.g., DNA encoding the constant domain of an antibody of thedesired isotype. See, e.g., Lantto et al., (2002) Methods Mol. Biol.178:303-16.

Accordingly, the antibodies that are provided include those comprising,for example, the variable domain combinations described, supra., havinga desired isotype (for example, IgA, IgG1, IgG2, IgG3, IgG4, IgE, andIgD) as well as Fab or F(ab′)₂ fragments thereof. Moreover, if an IgG4is desired, it can also be desired to introduce a point mutation (e.g.,a mutation from CPSCP to CPPCP (SEQ ID NOs 1828 and 1829, respectively,in order of appearance) in the hinge region as described in Bloom etal., (1997) Protein Science 6:407-15, incorporated by reference herein)to alleviate a tendency to form intra-H chain disulfide bonds that canlead to heterogeneity in the IgG4 antibodies.

Moreover, techniques for deriving antibodies having different properties(i.e., varying affinities for the antigen to which they bind) are alsoknown. One such technique, referred to as chain shuffling, involvesdisplaying immunoglobulin variable domain gene repertoires on thesurface of filamentous bacteriophage, often referred to as phagedisplay. Chain shuffling has been used to prepare high affinityantibodies to the hapten 2-phenyloxazol-5-one, as described by Marks etal., (1992) Nature Biotechnology 10:779-83.

Conservative modifications can be made to the heavy and light chainvariable regions described in Table 2, or the CDRs described in Tables3A and 3B, 4A and 4B, and Tables 6-23 (and corresponding modificationsto the encoding nucleic acids) to produce an antigen binding proteinhaving functional and biochemical characteristics. Methods for achievingsuch modifications are described herein.

Antigen binding proteins that specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3ccan be further modified in various ways. For example, if they are to beused for therapeutic purposes, they can be conjugated with polyethyleneglycol (PEGylated) to prolong the serum half-life or to enhance proteindelivery. PEG can be attached directly to the antigen binding protein orit can be attached via a linker, such as a glycosidic linkage.

Alternatively, the V region of the subject antibodies or fragmentsthereof can be fused with the Fc region of a different antibodymolecule. The Fc region used for this purpose can be modified so that itdoes not bind complement, thus reducing the likelihood of inducing celllysis in the patient when the fusion protein is used as a therapeuticagent. In addition, the subject antibodies or functional fragmentsthereof can be conjugated with human serum albumin to enhance the serumhalf-life of the antibody or fragment thereof. Another useful fusionpartner for the antigen binding proteins or fragments thereof istransthyretin (TTR). TTR has the capacity to form a tetramer, thus anantibody-TTR fusion protein can form a multivalent antibody which canincrease its binding avidity.

Alternatively, substantial modifications in the functional and/orbiochemical characteristics of the antigen binding proteins describedherein can be achieved by creating substitutions in the amino acidsequence of the heavy and light chains that differ significantly intheir effect on maintaining (a) the structure of the molecular backbonein the area of the substitution, for example, as a sheet or helicalconformation, (b) the charge or hydrophobicity of the molecule at thetarget site, or (c) the bulkiness of the side chain. A “conservativeamino acid substitution” can involve a substitution of a native aminoacid residue with a nonnative residue that has little or no effect onthe polarity or charge of the amino acid residue at that position. See,Table 8, supra. Furthermore, any native residue in the polypeptide canalso be substituted with alanine, as has been previously described foralanine scanning mutagenesis.

Amino acid substitutions (whether conservative or non-conservative) ofthe subject antibodies can be implemented by those skilled in the art byapplying routine techniques. Amino acid substitutions can be used toidentify important residues of the antibodies provided herein, or toincrease or decrease the affinity of these antibodies for a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c or for modifying the binding affinity of otherantigen-binding proteins described herein.

Methods of Expressing Antigen Binding Proteins

Expression systems and constructs in the form of plasmids, expressionvectors, transcription or expression cassettes that comprise at leastone polynucleotide as described above are also provided herein, as wellhost cells comprising such expression systems or constructs.

The antigen binding proteins provided herein can be prepared by any of anumber of conventional techniques. For example, antigen binding proteinsthat specifically bind to a complex comprising β-Klotho and at least oneof (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be produced byrecombinant expression systems, using any technique known in the art.See, e.g., Monoclonal Antibodies, Hybridomas: A New Dimension inBiological Analyses, (Kennet et al., eds.) Plenum Press (1980) andsubsequent editions; and Harlow & Lane, (1988) supra.

Antigen binding proteins can be expressed in hybridoma cell lines (e.g.,in particular antibodies can be expressed in hybridomas) or in celllines other than hybridomas. Expression constructs encoding theantibodies can be used to transform a mammalian, insect or microbialhost cell. Transformation can be performed using any known method forintroducing polynucleotides into a host cell, including, for examplepackaging the polynucleotide in a virus or bacteriophage and transducinga host cell with the construct by transfection procedures known in theart, as exemplified by U.S. Pat. Nos. 4,399,216; 4,912,040; 4,740,461;and 4,959,455. The optimal transformation procedure used will dependupon which type of host cell is being transformed. Methods forintroduction of heterologous polynucleotides into mammalian cells arewell known in the art and include, but are not limited to,dextran-mediated transfection, calcium phosphate precipitation,polybrene mediated transfection, protoplast fusion, electroporation,encapsulation of the polynucleotide(s) in liposomes, mixing nucleic acidwith positively-charged lipids, and direct microinjection of the DNAinto nuclei.

Recombinant expression constructs typically comprise a nucleic acidmolecule encoding a polypeptide comprising one or more of the following:one or more CDRs provided herein; a light chain constant region; a lightchain variable region; a heavy chain constant region (e.g., C_(H)1,C_(H)2 and/or C_(H)3); and/or another scaffold portion of an antigenbinding protein. These nucleic acid sequences are inserted into anappropriate expression vector using standard ligation techniques. In oneembodiment, the heavy or light chain constant region is appended to theC-terminus of the anti-β-Klotho/FGFR (e.g., FGFR1c, FGFR2c or FGFR3c)complex-specific heavy or light chain variable region and is ligatedinto an expression vector. The vector is typically selected to befunctional in the particular host cell employed (i.e., the vector iscompatible with the host cell machinery, permitting amplification and/orexpression of the gene can occur). In some embodiments, vectors are usedthat employ protein-fragment complementation assays using proteinreporters, such as dihydrofolate reductase (see, for example, U.S. Pat.No. 6,270,964, which is hereby incorporated by reference). Suitableexpression vectors can be purchased, for example, from Invitrogen LifeTechnologies or BD Biosciences. Other useful vectors for cloning andexpressing the antibodies and fragments include those described inBianchi and McGrew, (2003) Biotech. Biotechnol. Bioeng. 84:439-44, whichis hereby incorporated by reference. Additional suitable expressionvectors are discussed, for example, in “Gene Expression Technology,”Methods Enzymol., vol. 185, (Goeddel et al., ed.), (1990), AcademicPress.

Typically, expression vectors used in any of the host cells will containsequences for plasmid maintenance and for cloning and expression ofexogenous nucleotide sequences. Such sequences, collectively referred toas “flanking sequences” in certain embodiments will typically includeone or more of the following nucleotide sequences: a promoter, one ormore enhancer sequences, an origin of replication, a transcriptionaltermination sequence, a complete intron sequence containing a donor andacceptor splice site, a sequence encoding a leader sequence forpolypeptide secretion, a ribosome binding site, a polyadenylationsequence, a polylinker region for inserting the nucleic acid encodingthe polypeptide to be expressed, and a selectable marker element.

Optionally, an expression vector can contain a “tag”-encoding sequence,i.e., an oligonucleotide molecule located at the 5′ or 3′ end of anantigen binding protein coding sequence; the oligonucleotide sequenceencodes polyHis (such as hexaHis, HHHHHH (SEQ ID NO: 1830)), or another“tag” such as FLAG, HA (hemaglutinin influenza virus), or myc, for whichcommercially available antibodies exist. This tag is typically fused tothe polypeptide upon expression of the polypeptide, and can serve as ameans for affinity purification or detection of the antigen bindingprotein from the host cell. Affinity purification can be accomplished,for example, by column chromatography using antibodies against the tagas an affinity matrix. Optionally, the tag can subsequently be removedfrom the purified antigen binding protein by various means such as usingcertain peptidases for cleavage.

Flanking sequences can be homologous (i.e., from the same species and/orstrain as the host cell), heterologous (i.e., from a species other thanthe host cell species or strain), hybrid (i.e., a combination offlanking sequences from more than one source), synthetic or native. Assuch, the source of a flanking sequence can be any prokaryotic oreukaryotic organism, any vertebrate or invertebrate organism, or anyplant, provided that the flanking sequence is functional in, and can beactivated by, the host cell machinery.

Flanking sequences useful in the vectors can be obtained by any ofseveral methods well known in the art. Typically, flanking sequencesuseful herein will have been previously identified by mapping and/or byrestriction endonuclease digestion and can thus be isolated from theproper tissue source using the appropriate restriction endonucleases. Insome cases, the full nucleotide sequence of a flanking sequence can beknown. Here, the flanking sequence can be synthesized using the methodsdescribed herein for nucleic acid synthesis or cloning.

Whether all or only a portion of the flanking sequence is known, it canbe obtained using polymerase chain reaction (PCR) and/or by screening agenomic library with a suitable probe such as an oligonucleotide and/orflanking sequence fragment from the same or another species. Where theflanking sequence is not known, a fragment of DNA containing a flankingsequence can be isolated from a larger piece of DNA that can contain,for example, a coding sequence or even another gene or genes. Isolationcan be accomplished by restriction endonuclease digestion to produce theproper DNA fragment followed by isolation using agarose gelpurification, column chromatography or other methods known to theskilled artisan. The selection of suitable enzymes to accomplish thispurpose will be readily apparent to one of ordinary skill in the art.

An origin of replication is typically a part of those prokaryoticexpression vectors purchased commercially, and the origin aids in theamplification of the vector in a host cell. If the vector of choice doesnot contain an origin of replication site, one can be chemicallysynthesized based on a known sequence, and ligated into the vector. Forexample, the origin of replication from the plasmid pBR322 (GenBankAccession # J01749, New England Biolabs, Beverly, Mass.) is suitable formost gram-negative bacteria, and various viral origins (e.g., SV40,polyoma, adenovirus, vesicular stomatitus virus (VSV), orpapillomaviruses such as HPV or BPV) are useful for cloning vectors inmammalian cells. Generally, the origin of replication component is notneeded for mammalian expression vectors (for example, the SV40 origin isoften used only because it also contains the virus early promoter).

A transcription termination sequence is typically located 3′ to the endof a polypeptide coding region and serves to terminate transcription.Usually, a transcription termination sequence in prokaryotic cells is aG-C rich fragment followed by a poly-T sequence. While the sequence iseasily cloned from a library or even purchased commercially as part of avector, it can also be readily synthesized using methods for nucleicacid synthesis such as those described herein.

A selectable marker gene encodes a protein necessary for the survivaland growth of a host cell grown in a selective culture medium. Typicalselection marker genes encode proteins that (a) confer resistance toantibiotics or other toxins, e.g., ampicillin, tetracycline, orkanamycin for prokaryotic host cells; (b) complement auxotrophicdeficiencies of the cell; or (c) supply critical nutrients not availablefrom complex or defined media. Specific selectable markers are thekanamycin resistance gene, the ampicillin resistance gene, and thetetracycline resistance gene. Advantageously, a neomycin resistance genecan also be used for selection in both prokaryotic and eukaryotic hostcells.

Other selectable genes can be used to amplify the gene that will beexpressed. Amplification is the process wherein genes that are requiredfor production of a protein critical for growth or cell survival arereiterated in tandem within the chromosomes of successive generations ofrecombinant cells. Examples of suitable selectable markers for mammaliancells include dihydrofolate reductase (DHFR) and promoterless thymidinekinase genes. Mammalian cell transformants are placed under selectionpressure wherein only the transformants are uniquely adapted to surviveby virtue of the selectable gene present in the vector. Selectionpressure is imposed by culturing the transformed cells under conditionsin which the concentration of selection agent in the medium issuccessively increased, thereby leading to the amplification of both theselectable gene and the DNA that encodes another gene, such as anantigen binding protein that binds to a complex comprising β-Klotho andat least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. As a result,increased quantities of a polypeptide such as an antigen binding proteinare synthesized from the amplified DNA.

A ribosome-binding site is usually necessary for translation initiationof mRNA and is characterized by a Shine-Dalgarno sequence (prokaryotes)or a Kozak sequence (eukaryotes). The element is typically located 3′ tothe promoter and 5′ to the coding sequence of the polypeptide to beexpressed.

In some cases, such as where glycosylation is desired in a eukaryotichost cell expression system, one can manipulate the various pre- orpro-sequences to improve glycosylation or yield. For example, one canalter the peptidase cleavage site of a particular signal peptide, or addprosequences, which also can affect glycosylation. The final proteinproduct can have, in the −1 position (relative to the first amino acidof the mature protein), one or more additional amino acids incident toexpression, which may not have been totally removed. For example, thefinal protein product can have one or two amino acid residues found inthe peptidase cleavage site, attached to the amino-terminus.Alternatively, use of some enzyme cleavage sites can result in aslightly truncated form of the desired polypeptide, if the enzyme cutsat such area within the mature polypeptide.

Expression and cloning will typically contain a promoter that isrecognized by the host organism and operably linked to the moleculeencoding an antigen binding protein that specifically binds to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c. Promoters are untranscribed sequences located upstream(i.e., 5′) to the start codon of a structural gene (generally withinabout 100 to 1000 bp) that control transcription of the structural gene.Promoters are conventionally grouped into one of two classes: induciblepromoters and constitutive promoters. Inducible promoters initiateincreased levels of transcription from DNA under their control inresponse to some change in culture conditions, such as the presence orabsence of a nutrient or a change in temperature. Constitutivepromoters, on the other hand, uniformly transcribe a gene to which theyare operably linked, that is, with little or no control over geneexpression. A large number of promoters, recognized by a variety ofpotential host cells, are well known. A suitable promoter is operablylinked to the DNA encoding heavy chain or light chain comprising anantigen binding protein by removing the promoter from the source DNA byrestriction enzyme digestion and inserting the desired promoter sequenceinto the vector.

Suitable promoters for use with yeast hosts are also well known in theart. Yeast enhancers are advantageously used with yeast promoters.Suitable promoters for use with mammalian host cells are well known andinclude, but are not limited to, those obtained from the genomes ofviruses such as polyoma virus, fowlpox virus, adenovirus (such asAdenovirus 2), bovine papilloma virus, avian sarcoma virus,cytomegalovirus, retroviruses, hepatitis-B virus, and Simian Virus 40(SV40). Other suitable mammalian promoters include heterologousmammalian promoters, for example, heat-shock promoters and the actinpromoter.

Additional promoters which can be of interest include, but are notlimited to: SV40 early promoter (Benoist & Chambon, (1981) Nature290:304-310); CMV promoter (Thomsen et al., (1984) Proc. Natl. Acad.U.S.A. 81:659-663); the promoter contained in the 3′ long terminalrepeat of Rous sarcoma virus (Yamamoto et al., (1980) Cell 22:787-97);herpes thymidine kinase promoter (Wagner et al., (1981) Proc. Natl.Acad. Sci. U.S.A. 78:1444-45); promoter and regulatory sequences fromthe metallothionine gene (Prinster et al., (1982) Nature 296:39-42); andprokaryotic promoters such as the beta-lactamase promoter(Villa-Kamaroff et al., (1978) Proc. Natl. Acad. Sci. U.S.A.75:3727-31); or the tac promoter (DeBoer et al., (1983) Proc. Natl.Acad. Sci. U.S.A. 80:21-25). Also of interest are the following animaltranscriptional control regions, which exhibit tissue specificity andhave been utilized in transgenic animals: the elastase I gene controlregion that is active in pancreatic acinar cells (Swift et al., (1984)Cell 38:639-46; Ornitz et al., (1986) Cold Spring Harbor Symp. Quant.Biol. 50:399-409; MacDonald, (1987) Hepatology 7:425-515); the insulingene control region that is active in pancreatic beta cells (Hanahan,(1985) Nature 315:115-22); the immunoglobulin gene control region thatis active in lymphoid cells (Grosschedl et al., (1984) Cell 38:647-58;Adames et al., (1985) Nature 318:533-38; Alexander et al., (1987) Mol.Cell. Biol. 7:1436-44); the mouse mammary tumor virus control regionthat is active in testicular, breast, lymphoid and mast cells (Leder etal., (1986) Cell 45:485-95); the albumin gene control region that isactive in liver (Pinkert et al., (1987) Genes and Devel. 1:268-76); thealpha-feto-protein gene control region that is active in liver (Krumlaufet al., (1985) Mol. Cell. Biol. 5:1639-48; Hammer et al., (1987) Science253:53-58); the alpha 1-antitrypsin gene control region that is activein liver (Kelsey et al., (1987) Genes and Devel. 1:161-71); thebeta-globin gene control region that is active in myeloid cells (Mogramet al., (1985) Nature 315:338-40; Kollias et al., (1986) Cell 46:89-94);the myelin basic protein gene control region that is active inoligodendrocyte cells in the brain (Readhead et al., (1987) Cell48:703-12); the myosin light chain-2 gene control region that is activein skeletal muscle (Sani, (1985) Nature 314:283-86); and thegonadotropic releasing hormone gene control region that is active in thehypothalamus (Mason et al., (1986) Science 234:1372-78).

An enhancer sequence can be inserted into the vector to increasetranscription of DNA encoding light chain or heavy chain comprising anantigen binding protein that specifically binds to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c byhigher eukaryotes, e.g., a human antigen binding protein thatspecifically binds to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Enhancers are cis-actingelements of DNA, usually about 10-300 bp in length, that act on thepromoter to increase transcription. Enhancers are relatively orientationand position independent, having been found at positions both 5′ and 3′to the transcription unit. Several enhancer sequences available frommammalian genes are known (e.g., globin, elastase, albumin,alpha-feto-protein and insulin). Typically, however, an enhancer from avirus is used. The SV40 enhancer, the cytomegalovirus early promoterenhancer, the polyoma enhancer, and adenovirus enhancers known in theart are exemplary enhancing elements for the activation of eukaryoticpromoters. While an enhancer can be positioned in the vector either 5′or 3′ to a coding sequence, it is typically located at a site 5′ fromthe promoter. A sequence encoding an appropriate native or heterologoussignal sequence (leader sequence or signal peptide) can be incorporatedinto an expression vector, to promote extracellular secretion of theantibody. The choice of signal peptide or leader depends on the type ofhost cells in which the antibody is to be produced, and a heterologoussignal sequence can replace the native signal sequence. Examples ofsignal peptides that are functional in mammalian host cells include thefollowing: the signal sequence for interleukin-7 (IL-7) described inU.S. Pat. No. 4,965,195; the signal sequence for interleukin-2 receptordescribed in Cosman et al., (1984) Nature 312:768-71; the interleukin-4receptor signal peptide described in EP Patent No. 0367 566; the type Iinterleukin-1 receptor signal peptide described in U.S. Pat. No.4,968,607; the type II interleukin-1 receptor signal peptide describedin EP Patent No. 0 460 846.

Expression vectors can be constructed from a starting vector such as acommercially available vector. Such vectors can but need not contain allof the desired flanking sequences. Where one or more of the flankingsequences are not already present in the vector, they can beindividually obtained and ligated into the vector. Methods used forobtaining each of the flanking sequences are well known to one skilledin the art.

After the vector has been constructed and a nucleic acid moleculeencoding light chain, a heavy chain, or a light chain and a heavy chaincomprising an antigen binding protein that specifically binds to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c has been inserted into the proper site of the vector,the completed vector can be inserted into a suitable host cell foramplification and/or polypeptide expression. The transformation of anexpression vector for an antigen binding protein into a selected hostcell can be accomplished by well known methods including transfection,infection, calcium phosphate co-precipitation, electroporation,microinjection, lipofection, DEAE-dextran mediated transfection, orother known techniques. The method selected will in part be a functionof the type of host cell to be used. These methods and other suitablemethods are well known to the skilled artisan, and are set forth, forexample, in Sambrook et al., (2001), supra.

A host cell, when cultured under appropriate conditions, synthesizes anantigen binding protein that can subsequently be collected from theculture medium (if the host cell secretes it into the medium) ordirectly from the host cell producing it (if it is not secreted). Theselection of an appropriate host cell will depend upon various factors,such as desired expression levels, polypeptide modifications that aredesirable or necessary for activity (such as glycosylation orphosphorylation) and ease of folding into a biologically activemolecule.

Mammalian cell lines available as hosts for expression are well known inthe art and include, but are not limited to, immortalized cell linesavailable from the American Type Culture Collection (ATCC), includingbut not limited to HeLa cells, Human Embryonic Kidney 293 cells (HEK293cells), Chinese hamster ovary (CHO) cells, HeLa cells, baby hamsterkidney (BHK) cells, monkey kidney cells (COS), human hepatocellularcarcinoma cells (e.g., Hep G2), and a number of other cell lines. Incertain embodiments, cell lines can be selected through determiningwhich cell lines have high expression levels and constitutively produceantigen binding proteins with desirable binding properties (e.g., theability to bind to a complex comprising β-Klotho and at least one of (i)FGFR1c, (ii) FGFR2c and (iii) FGFR3c). In another embodiment, a cellline from the B cell lineage that does not make its own antibody but hasa capacity to make and secrete a heterologous antibody can be selected.The ability to induce FGF21-like signaling can also form a selectioncriterion.

Uses of Antigen Binding Proteins for Diagnostic and Therapeutic Purposes

The antigen binding proteins disclosed herein are useful for detectingto a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii)FGFR2c and (iii) FGFR3c in biological samples and identification ofcells or tissues that produce one or more of β-Klotho and at least oneof (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. For instance, the antigenbinding proteins disclosed herein can be used in diagnostic assays,e.g., binding assays to detect and/or quantify a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3cexpressed in a tissue or cell.

Antigen binding proteins that specifically bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3ccan also be used in treatment of diseases related to FGF21-likesignaling in a patient in need thereof, such as type 2 diabetes,obesity, dyslipidemia, NASH, cardiovascular disease, and metabolicsyndrome. By forming a signaling complex comprising an antigen bindingprotein and a complex comprising β-Klotho and at least one of (i)FGFR1c, (ii) FGFR2c and (iii) FGFR3c, the natural in vivo activity ofFGF21, which associates with a complex comprising β-Klotho and at leastone of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in vivo to initiatesignaling, can be mimicked and/or enhanced, leading to therapeuticeffects.

Indications

A disease or condition associated with human FGF21 includes any diseaseor condition whose onset in a patient is influenced by, at least inpart, the lack of or therapeutically insufficient induction ofFGF21-like signaling, which is initiated in vivo by the formation of acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c. The severity of the disease or condition can also bedecreased by the induction of FGF21-like signaling. Examples of diseasesand conditions that can be treated with the antigen binding proteinsprovided herein include type 2 diabetes, obesity, dyslipidemia, NASH,cardiovascular disease, and metabolic syndrome.

The antigen binding proteins described herein can be used to treat type2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, andmetabolic syndrome, or can be employed as a prophylactic treatmentadministered, e.g., daily, weekly, biweekly, monthly, bimonthly,biannually, etc to prevent or reduce the frequency and/or severity ofsymptoms, e.g., elevated plasma glucose levels, elevated triglyceridesand/or cholesterol levels, thereby providing an improved glycemic andcardiovascular risk factor profile.

Diagnostic Methods

The antigen binding proteins described herein can be used for diagnosticpurposes to detect, diagnose, or monitor diseases and/or conditionsassociated with FGFR1c, FGFR2c, FGFR3c, β-Klotho, FGF21 and/or complexescomprising combinations thereof. Also provided are methods for thedetection of the presence of to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in a sample usingclassical immunohistological methods known to those of skill in the art(e.g., Tijssen, (1985) “Practice and Theory of Enzyme Immunoassays” inLaboratory Techniques in Biochemistry and Molecular Biology, 15 (Burdon& van Knippenberg, eds.), Elsevier Biomedical); Zola, (1987) MonoclonalAntibodies: A Manual of Techniques, pp. 147-58 (CRC Press, Inc.);Jalkanen et al., (1985) J. Cell. Biol. 101:976-85; Jalkanen et al.,(1987) J. Cell Biol. 105:3087-96). The detection of a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3ccan be performed in vivo or in vitro.

Diagnostic applications provided herein include use of the antigenbinding proteins to detect expression/formation of a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c,and/or binding to a complex comprising β-Klotho and at least one of (i)FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Examples of methods useful in thedetection of the presence of a complex comprising β-Klotho and at leastone of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c include immunoassays,such as the enzyme linked immunosorbent assay (ELISA) and theradioimmunoassay (RIA).

For diagnostic applications, the antigen binding protein typically willbe labeled with a detectable labeling group. Suitable labeling groupsinclude, but are not limited to, the following: radioisotopes orradionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I),fluorescent groups (e.g., FITC, rhodamine, lanthanide phosphors),enzymatic groups (e.g., horseradish peroxidase, β-galactosidase,luciferase, alkaline phosphatase), chemiluminescent groups, biotinylgroups, or predetermined polypeptide epitopes recognized by a secondaryreporter (e.g., leucine zipper pair sequences, binding sites forsecondary antibodies, metal binding domains, epitope tags). In someembodiments, the labeling group is coupled to the antigen bindingprotein via spacer arms of various lengths to reduce potential sterichindrance. Various methods for labeling proteins are known in the artand can be used.

In another aspect, an antigen binding protein can be used to identify acell or cells that express a complex comprising β-Klotho and at leastone of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In a specificembodiment, the antigen binding protein is labeled with a labeling groupand the binding of the labeled antigen binding protein to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c is detected. In a further specific embodiment, the bindingof the antigen binding protein to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c detected in vivo.In a further specific embodiment, the antigen binding protein isisolated and measured using techniques known in the art. See, forexample, Harlow & Lane, (1988) supra; Current Protocols In Immunology(John E. Coligan, ed), John Wiley & Sons (1993 ed., and supplementsand/or updates). Another aspect provides for detecting the presence of atest molecule that competes for binding to a complex comprising β-Klothoand at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with theantigen binding proteins provided, as disclosed herein. An example ofone such assay could involve detecting the amount of free antigenbinding protein in a solution containing an amount of a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c in the presence or absence of the test molecule. Anincrease in the amount of free antigen binding protein (i.e., theantigen binding protein not bound to a complex comprising β-Klotho andat least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c) would indicatethat the test molecule is capable of competing for binding to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c with the antigen binding protein. In one embodiment, theantigen binding protein is labeled with a labeling group. Alternatively,the test molecule is labeled and the amount of free test molecule ismonitored in the presence and absence of an antigen binding protein.

Methods of Treatment: Pharmaceutical Formulations and Routes ofAdministration

Methods of using the disclosed antigen binding proteins are alsoprovided. In some methods, an antigen binding protein is provided to apatient, which induces FGF21-like signaling.

Pharmaceutical compositions that comprise a therapeutically effectiveamount of one or a plurality of the antigen binding proteins and apharmaceutically acceptable diluent, carrier, solubilizer, emulsifier,preservative, and/or adjuvant are also provided. In addition, methods oftreating a patient by administering such pharmaceutical composition areincluded. The term “patient” includes human patients.

Acceptable formulation materials are nontoxic to recipients at thedosages and concentrations employed. In specific embodiments,pharmaceutical compositions comprising a therapeutically effectiveamount of human antigen binding proteins that specifically bind to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c are provided.

In certain embodiments, acceptable formulation materials preferably arenontoxic to recipients at the dosages and concentrations employed. Incertain embodiments, the pharmaceutical composition can containformulation materials for modifying, maintaining or preserving, forexample, the pH, osmolarity, viscosity, clarity, color, isotonicity,odor, sterility, stability, rate of dissolution or release, adsorptionor penetration of the composition. In such embodiments, suitableformulation materials include, but are not limited to, amino acids (suchas glycine, glutamine, asparagine, arginine or lysine); antimicrobials;antioxidants (such as ascorbic acid, sodium sulfite or sodiumhydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCl,citrates, phosphates or other organic acids); bulking agents (such asmannitol or glycine); chelating agents (such as ethylenediaminetetraacetic acid (EDTA)); complexing agents (such as caffeine,polyvinylpyrrolidone, beta-cyclodextrin orhydroxypropyl-beta-cyclodextrin); fillers; monosaccharides;disaccharides; and other carbohydrates (such as glucose, mannose ordextrins); proteins (such as serum albumin, gelatin or immunoglobulins);coloring, flavoring and diluting agents; emulsifying agents; hydrophilicpolymers (such as polyvinylpyrrolidone); low molecular weightpolypeptides; salt-forming counterions (such as sodium); preservatives(such as benzalkonium chloride, benzoic acid, salicylic acid,thimerosal, phenethyl alcohol, methylparaben, propylparaben,chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such asglycerin, propylene glycol or polyethylene glycol); sugar alcohols (suchas mannitol or sorbitol); suspending agents; surfactants or wettingagents (such as Pluronics, PEG, sorbitan esters, polysorbates such aspolysorbate 20, polysorbate, triton, tromethamine, lecithin,cholesterol, tyloxapal); stability enhancing agents (such as sucrose orsorbitol); tonicity enhancing agents (such as alkali metal halides,preferably sodium or potassium chloride, mannitol sorbitol); deliveryvehicles; diluents; excipients and/or pharmaceutical adjuvants. See,e.g., Remington's Pharmaceutical Sciences, 18th Edition, (A. R. Gennaro,ed.), 1990, Mack Publishing Company, and subsequent editions.

In certain embodiments, the optimal pharmaceutical composition will bedetermined by one skilled in the art depending upon, for example, theintended route of administration, delivery format and desired dosage.See, for example, Remington's Pharmaceutical Sciences, supra. In certainembodiments, such compositions can influence the physical state,stability, rate of in vivo release and rate of in vivo clearance of theantigen binding proteins disclosed. In certain embodiments, the primaryvehicle or carrier in a pharmaceutical composition can be either aqueousor non-aqueous in nature. For example, a suitable vehicle or carrier canbe water for injection, physiological saline solution or artificialcerebrospinal fluid, possibly supplemented with other materials commonin compositions for parenteral administration. Neutral buffered salineor saline mixed with serum albumin are further exemplary vehicles. Inspecific embodiments, pharmaceutical compositions comprise Tris bufferof about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, and canfurther include sorbitol or a suitable substitute. In certainembodiments, compositions comprising antigen binding proteins thatspecifically bind to a complex comprising β-Klotho and at least one of(i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be prepared for storage bymixing the selected composition having the desired degree of purity withoptional formulation agents (see, Remington's Pharmaceutical Sciences,supra for examples of suitable formulation agents) in the form of alyophilized cake or an aqueous solution. Further, in certainembodiments, antigen binding proteins that bind to a complex comprisingβ-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3ccan be formulated as a lyophilizate using appropriate excipients such assucrose. The pharmaceutical compositions can be selected for parenteraldelivery.

Alternatively, the compositions can be selected for inhalation or fordelivery through the digestive tract, such as orally. Preparation ofsuch pharmaceutically acceptable compositions is within the skill of theart.

The formulation components are present preferably in concentrations thatare acceptable to the site of administration. In certain embodiments,buffers are used to maintain the composition at physiological pH or at aslightly lower pH, typically within a pH range of from about 5 to about8.

When parenteral administration is contemplated, the therapeuticcompositions can be provided in the form of a pyrogen-free, parenterallyacceptable aqueous solution comprising the desired antigen bindingprotein in a pharmaceutically acceptable vehicle. A particularlysuitable vehicle for parenteral injection is sterile distilled water inwhich the antigen binding protein is formulated as a sterile, isotonicsolution, properly preserved. In certain embodiments, the preparationcan involve the formulation of the desired molecule with an agent, suchas injectable microspheres, bio-erodible particles, polymeric compounds(such as polylactic acid or polyglycolic acid), beads or liposomes, thatcan provide controlled or sustained release of the product which can bedelivered via depot injection. In certain embodiments, hyaluronic acidcan also be used, which can have the effect of promoting sustainedduration in the circulation. In certain embodiments, implantable drugdelivery devices can be used to introduce the desired antigen bindingprotein.

Certain pharmaceutical compositions are formulated for inhalation. Insome embodiments, antigen binding proteins that bind to a complexcomprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and(iii) FGFR3c are formulated as a dry, inhalable powder. In specificembodiments, antigen binding protein inhalation solutions can also beformulated with a propellant for aerosol delivery. In certainembodiments, solutions can be nebulized. Pulmonary administration andformulation methods therefore are further described in InternationalPatent Application No. PCT/US94/001875, which is incorporated byreference and describes pulmonary delivery of chemically modifiedproteins. Some formulations can be administered orally. Antigen bindingproteins that specifically bind to a complex comprising β-Klotho and atleast one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that areadministered in this fashion can be formulated with or without carrierscustomarily used in the compounding of solid dosage forms such astablets and capsules. In certain embodiments, a capsule can be designedto release the active portion of the formulation at the point in thegastrointestinal tract when bioavailability is maximized andpre-systemic degradation is minimized. Additional agents can be includedto facilitate absorption of an antigen binding protein. Diluents,flavorings, low melting point waxes, vegetable oils, lubricants,suspending agents, tablet disintegrating agents, and binders can also beemployed.

Some pharmaceutical compositions comprise an effective quantity of oneor a plurality of human antigen binding proteins that specifically bindto a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii)FGFR2c and (iii) FGFR3c in a mixture with non-toxic excipients that aresuitable for the manufacture of tablets. By dissolving the tablets insterile water, or another appropriate vehicle, solutions can be preparedin unit-dose form. Suitable excipients include, but are not limited to,inert diluents, such as calcium carbonate, sodium carbonate orbicarbonate, lactose, or calcium phosphate; or binding agents, such asstarch, gelatin, or acacia; or lubricating agents such as magnesiumstearate, stearic acid, or talc.

Additional pharmaceutical compositions will be evident to those skilledin the art, including formulations involving antigen binding proteinsthat specifically bind to a complex comprising β-Klotho and at least oneof (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in sustained- orcontrolled-delivery formulations. Techniques for formulating a varietyof other sustained- or controlled-delivery means, such as liposomecarriers, bio-erodible microparticles or porous beads and depotinjections, are also known to those skilled in the art. See, forexample, International Patent Application No. PCT/US93/00829, which isincorporated by reference and describes controlled release of porouspolymeric microparticles for delivery of pharmaceutical compositions.Sustained-release preparations can include semipermeable polymermatrices in the form of shaped articles, e.g., films, or microcapsules.Sustained release matrices can include polyesters, hydrogels,polylactides (as disclosed in U.S. Pat. No. 3,773,919 and EuropeanPatent Application Publication No. EP 058481, each of which isincorporated by reference), copolymers of L-glutamic acid and gammaethyl-L-glutamate (Sidman et al., (1983) Biopolymers 2:547-556), poly(2-hydroxyethyl-inethacrylate) (Langer et al., (1981) J. Biomed. Mater.Res. 15:167-277 and Langer, (1982) Chem. Tech. 12:98-105), ethylenevinyl acetate (Langer et al., (1981) supra) orpoly-D(−)-3-hydroxybutyric acid (European Patent Application PublicationNo. EP 133988). Sustained release compositions can also includeliposomes that can be prepared by any of several methods known in theart. See, e.g., Eppstein et al., (1985) Proc. Natl. Acad. Sci. U.S.A.82:3688-3692; European Patent Application Publication Nos. EP 036676; EP088046 and EP 143949, incorporated by reference.

Pharmaceutical compositions used for in vivo administration aretypically provided as sterile preparations. Sterilization can beaccomplished by filtration through sterile filtration membranes. Whenthe composition is lyophilized, sterilization using this method can beconducted either prior to or following lyophilization andreconstitution. Compositions for parenteral administration can be storedin lyophilized form or in a solution. Parenteral compositions generallyare placed into a container having a sterile access port, for example,an intravenous solution bag or vial having a stopper pierceable by ahypodermic injection needle.

In certain embodiments, cells expressing a recombinant antigen bindingprotein as disclosed herein are encapsulated for delivery (see, Tao etal., Invest. Ophthalmol Vis Sci (2002) 43:3292-3298 and Sieving et al.,Proc. Natl. Acad. Sciences USA (2006) 103:3896-3901).

In certain formulations, an antigen binding protein has a concentrationof between 10 mg/ml and 150 mg/ml. Some formulations contain a buffer,sucrose and polysorbate. An example of a formulation is one containing50-100 mg/ml of antigen binding protein, 5-20 mM sodium acetate, 5-10%w/v sucrose, and 0.002-0.008% w/v polysorbate. Certain, formulations,for instance, contain 1-100 mg/ml of an antigen binding protein in 9-11mM sodium acetate buffer, 8-10% w/v sucrose, and 0.005-0.006% w/vpolysorbate. The pH of certain such formulations is in the range of4.5-6. Other formulations can have a pH of 5.0-5.5.

Once the pharmaceutical composition has been formulated, it can bestored in sterile vials as a solution, suspension, gel, emulsion, solid,crystal, or as a dehydrated or lyophilized powder. Such formulations canbe stored either in a ready-to-use form or in a form (e.g., lyophilized)that is reconstituted prior to administration. Kits for producing asingle-dose administration unit are also provided. Certain kits containa first container having a dried protein and a second container havingan aqueous formulation. In certain embodiments, kits containing singleand multi-chambered pre-filled syringes (e.g., liquid syringes andlyosyringes) are provided. The therapeutically effective amount of anantigen binding protein-containing pharmaceutical composition to beemployed will depend, for example, upon the therapeutic context andobjectives. One skilled in the art will appreciate that the appropriatedosage levels for treatment will vary depending, in part, upon themolecule delivered, the indication for which the antigen binding proteinis being used, the route of administration, and the size (body weight,body surface or organ size) and/or condition (the age and generalhealth) of the patient. In certain embodiments, the clinician can titerthe dosage and modify the route of administration to obtain the optimaltherapeutic effect.

A typical dosage can range from about 1 μg/kg to up to about 30 mg/kg ormore, depending on the factors mentioned above. In specific embodiments,the dosage can range from 10 μg/kg up to about 35 mg/kg, optionally from0.1 mg/kg up to about 35 mg/kg, alternatively from 0.3 mg/kg up to about20 mg/kg. In some applications, the dosage is from 0.5 mg/kg to 20 mg/kgand in other applications the dosage is from 21-100 mg/kg. In someinstances, an antigen binding protein is dosed at 0.3-20 mg/kg. Thedosage schedule in some treatment regimes is at a dose of 0.3 mg/kgqW-20 mg/kg qW.

Dosing frequency will depend upon the pharmacokinetic parameters of theparticular antigen binding protein in the formulation used. Typically, aclinician administers the composition until a dosage is reached thatachieves the desired effect. The composition can therefore beadministered as a single dose, or as two or more doses (which can butneed not contain the same amount of the desired molecule) over time, oras a continuous infusion via an implantation device or catheter.Appropriate dosages can be ascertained through use of appropriatedose-response data. In certain embodiments, the antigen binding proteinscan be administered to patients throughout an extended time period.Chronic administration of an antigen binding protein minimizes theadverse immune or allergic response commonly associated with antigenbinding proteins that are not fully human, for example an antibodyraised against a human antigen in a non-human animal, for example, anon-fully human antibody or non-human antibody produced in a non-humanspecies.

The route of administration of the pharmaceutical composition is inaccord with known methods, e.g., orally, through injection byintravenous, intraperitoneal, intracerebral (intra-parenchymal),intracerebroventricular, intramuscular, intra-ocular, intraarterial,intraportal, or intralesional routes; by sustained release systems or byimplantation devices. In certain embodiments, the compositions can beadministered by bolus injection or continuously by infusion, or byimplantation device.

The composition also can be administered locally via implantation of amembrane, sponge or another appropriate material onto which the desiredmolecule has been absorbed or encapsulated. In certain embodiments,where an implantation device is used, the device can be implanted intoany suitable tissue or organ, and delivery of the desired molecule canbe via diffusion, timed-release bolus, or continuous administration.

It also can be desirable to use antigen binding protein pharmaceuticalcompositions ex vivo. In such instances, cells, tissues or organs thathave been removed from the patient are exposed to antigen bindingprotein pharmaceutical compositions after which the cells, tissuesand/or organs are subsequently implanted back into the patient.

In particular, antigen binding proteins that specifically bind to acomplex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2cand (iii) FGFR3c can be delivered by implanting certain cells that havebeen genetically engineered, using methods such as those describedherein and known in the art, to express and secrete the polypeptide. Incertain embodiments, such cells can be animal or human cells, and can beautologous, heterologous, or xenogeneic. In certain embodiments, thecells can be immortalized. In other embodiments, in order to decreasethe chance of an immunological response, the cells can be encapsulatedto avoid infiltration of surrounding tissues. In further embodiments,the encapsulation materials are typically biocompatible, semi-permeablepolymeric enclosures or membranes that allow the release of the proteinproduct(s) but prevent the destruction of the cells by the patient'simmune system or by other detrimental factors from the surroundingtissues.

Combination Therapies

In another aspect, the present disclosure provides a method of treatinga subject for diabetes with a therapeutic antigen binding protein of thepresent disclosure, such as the fully human therapeutic antibodiesdescribed herein, together with one or more other treatments. In oneembodiment, such a combination therapy achieves an additive orsynergistic effect. The antigen binding proteins can be administered incombination with one or more of the type 2 diabetes or obesitytreatments currently available. These treatments for diabetes includebiguanide (metaformin), and sulfonylureas (such as glyburide,glipizide). Additional treatments directed at maintaining glucosehomeostasis include PPAR gamma agonists (pioglitazone, rosiglitazone);glinides (meglitinide, repaglinide, and nateglinide); DPP-4 inhibitors(Januvia® and Onglyza®) and alpha glucosidase inhibitors (acarbose,voglibose).

Additional combination treatments for diabetes include injectabletreatments such as insulin and incretin mimetics (Byetta®, Exenatide®),other GLP-1 (glucagon-like peptide) analogs such as Victoza®(liraglutide), other GLP-1R agonists and Symlin® (pramlintide).

Additional combination treatments directed at weight loss includeMeridia® and Xenical®.

EXAMPLES

The following examples, including the experiments conducted and theresults achieved, are provided for illustrative purposes only and arenot to be construed as limiting.

Example 1 Preparation of FGFR1c and β-Klotho Over Expressing Cells forUse as an Antigen

Nucleic acid sequences encoding the full length human FGFR1cpolypepetide (SEQ ID NO: 4; FIGS. 1A-1B) and a separate sequenceencoding the full length human β-Klotho polypeptide (SEQ ID NO: 7; FIGS.2A-2C) were subcloned into suitable mammalian cell expression vectors(e.g., pcDNA3.1 Zeo, pcDNA3.1 Hyg (Invitrogen, Carlsbad, Calif.) orpDSRa24. The pDSRa24 vector contains SV40 early promoter/enhancer forexpressing the gene of interest and a mouse DHFR expression cassette forselection in CHO DHFR (−) host cells such as AM1/D CHO (a derivative ofDG44, CHO DHFR (−)).

AM-1/D CHO cells were transfected with linearized DNAs of huFGFR1c andhufβ-Klotho in standard mammalian cell expression vectors e.g. pcDNA3.1puro and pcDNA3.1 Hyg with Lipofectamine 2000 (Invitrogen, CarlsbadCalif.). The transfected cells were trypsinized 2 days aftertransfection and seeded into media containing the correspondingselection drugs i.e. puromycin and hygromycin. After 2 weeks, theresulting transfected colonies were trypsinized and pooled. Single cellclones from the pools were isolated and screened with antibodies tohuFGFR1c and huβKlotho in FACS and Clone 16 was selected due to the highlevel and balanced expression of the two receptor components.

2×10e9 fresh cells from Clone 16 were harvested from roller bottles intoa smaller volume in PBS and incubated with 10 μg/ml recombinant FGF21(Amgen, Thousand Oaks Calif.) at 4 C for 1 hours to form complex withthe cell surface receptors. The cells were washed twice with cold PBS,pelleted by centrifugation and frozen in individual vials at 2×10e8cells for immunization.

HEK 293T cells were transfected with DNA expressing a truncated versionof huFGFR1c (a signal peptide V_(H)21 was joined to the remaining FGFR1cfrom amino acid residue #141 to #822 (in SEQ ID NO: 4) with a deletionthat removed both the D1 domain and the acidic box (AB) and DNAexpressing the full length huβ-Klotho in pcDNA3.1 series or pTT5 (anexpression vector developed by Durocher, NRCC, with CMV promoter and EBVori) based vector for transient expression. The removal of the D1-AB onFGFR1c was designed to expose epitopes on FGFR1c (e.g., in the D2 and D3domains) that may be masked by this auto-inhibitory domain (seeMohammadi et al., (2005) Cytokine Growth Factor Reviews, 16, 107-137;Gupte et al., (2011) J. Mol. Biol. 408:491-502).

The expression of β-Klotho and truncated FGFR1c in the transfected 293Tcells was verified by the respective specific antibodies in FACS andcells were harvested on day 3 post-transfection and frozen as cellpellet into aliquots for immunization.

Stable CHO or transiently transfected HEK 293T cells expressing FGFR1cand β-Klotho individually or together were also generated and used fortitering mouse sera by FACS after immunization and for binding screensof the hybridoma supernatants by FMAT (see Example 3).

Example 2 Preparation of Monoclonal Antibodies

Immunizations were conducted using one or more suitable forms of FGF21receptor antigen, including: (1) cell-bound receptor of CHOtransfectants expressing full length human FGFR1c and β-Klotho at thecell surface, obtained by transfecting CHO cells with cDNA encoding ahuman full length FGFR1c polypeptide of SEQ ID NO: 4 (see also FIGS.1a-b ) and cDNA encoding a human β-Klotho polypeptide of SEQ ID NO: 7(see also FIGS. 2a-c ) in a balanced ratio with cells and incubated withFGF21 prior to freezing; (2) cell-bound receptor of 293T transfectantsexpressing full length human β-Klotho and an N-terminal truncated formof human FGFR1c encompassing amino acid residues 141-822 polypeptide ofSEQ ID NO: 4 (D1 domain of FGFR1c deleted).

A suitable amount of immunogen (i.e., 3-4×10⁶ cells/mouse of stablytransfected CHO cells or transiently transfected 293T cells mentionedabove was used for initial immunization in XENOMOUSE® according to themethods disclosed in U.S. patent application Ser. No. 08/759,620, filedDec. 3, 1996 and International Patent Application Nos. WO 98/24893, andWO 00/76310, the disclosures of which are incorporated by reference.Following the initial immunization, subsequent boost immunizations ofimmunogen (1.7×10⁶ FGF21R transfected cells/mouse) were administered ona schedule and for the duration necessary to induce a suitableanti-FGF21R titer in the mice. Titers were determined by a suitablemethod, for example, by enzyme immunoassay, fluorescence activated cellsorting (FACS), or by other methods (including combinations of enzymeimmunoassays and FACS).

Animals exhibiting suitable titers were identified, and lymphocytes wereobtained from draining lymph nodes and, if necessary, pooled for eachcohort. Lymphocytes were dissociated from lymphoid tissue by grinding ina suitable medium (for example, Dulbecco's Modified Eagle Medium; DMEM;obtainable from Invitrogen, Carlsbad, Calif.) to release the cells fromthe tissues, and suspended in DMEM. B cells were selected and/orexpanded using standard methods, and fused with suitable fusion partner,for example, nonsecretory myeloma P3X63Ag8.653 cells (American TypeCulture Collection CRL 1580; Kearney et al, (1979) J. Immunol.123:1548-1550), using techniques that were known in the art.

In one suitable fusion method, lymphocytes were mixed with fusionpartner cells at a ratio of 1:4. The cell mixture was gently pelleted bycentrifugation at 400×g for 4 minutes, the supernatant decanted, and thecell mixture gently mixed (for example, by using a 1 ml pipette). Fusionwas induced with PEG/DMSO (polyethylene glycol/dimethyl sulfoxide;obtained from Sigma-Aldrich, St. Louis Mo.; 1 ml per million oflymphocytes). PEG/DMSO was slowly added with gentle agitation over oneminute followed, by one minute of mixing. IDMEM (DMEM without glutamine;2 ml per million of B cells), was then added over 2 minutes with gentleagitation, followed by additional IDMEM (8 ml per million B-cells) whichwas added over 3 minutes.

The fused cells were pelleted (400×g 6 minutes) and resuspended in 20 mlSelection media (for example, DMEM containing Azaserine and Hypoxanthine[HA] and other supplemental materials as necessary) per million B-cells.Cells were incubated for 20-30 minutes at 37° C. and then resuspended in200 ml selection media and cultured for three to four days in T175flasks prior to 96 well plating.

Cells were distributed into 96-well plates using standard techniques tomaximize clonality of the resulting colonies. An alternative method wasalso employed and the fused cells were directly plated clonally into384-well plates to ensure monoclonality from the start. After severaldays of culture, supernatants were collected and subjected to screeningassays as detailed in the examples below, including confirmation ofbinding to human FGF21 receptor, specificity and/or cross-speciesreactivity. Positive cells were further selected and subjected tostandard cloning and subcloning techniques. Clonal lines were expandedin vitro, and the secreted human antibodies obtained for analysis.

In this manner, mice were immunized with cells expressing full lengthFGF21R cells mixed with FGF21, or cells expressing a truncated FGFR1cand full length β-Klotho, with a range of 11-17 immunizations over aperiod of approximately one to three and one-half months. Several celllines secreting FGF21R-specific antibodies were obtained, and theantibodies were further characterized. The sequences thereof arepresented herein and in the Sequence Listing, and results of varioustests using these antibodies are provided.

Example 3 Selection of Binding Antibodies by FMAT

After 14 days of culture, hybridoma supernatants were screened forFGF21R-specific monoclonal antibodies by Fluorometric Microvolume AssayTechnology (FMAT) by screening against either the CHO AM1/D/huFGF21Rcell line or recombinant HEK293 cells that were transfected with humanFGF21R and counter-screening against parental CHO or HEK293 cells.Briefly the cells in Freestyle media (Invitrogen) were seeded into384-well FMAT plates in a volume of 50 μL/well at a density of 4,000cells/well for the stable transfectants, and at a density of 16,000cells/well for the parental cells, and cells were incubated overnight at37° C. 10 μL/well of supernatant was then added, and the plates wereincubated for approximately one hour at 4° C., after which 10 μL/well ofanti-human IgG-Cy5 secondary antibody was added at a concentration of2.8 μg/ml (400 ng/ml final concentration). Plates were then incubatedfor one hour at 4° C., and fluorescence was read using an FMAT CellularDetection System (Applied Biosystems).

In total, over 1,500 hybridoma supernatants were identified as bindingto the FGF21 receptor expressing cells but not to parental cells by theFMAT method. These supernatants were then tested in the FGF21 functionalassays as described below.

Example 4 Selection of Antibodies that Induce FGF21-Like Signaling

Experiments were performed to identify functional antibodies that mimicwild-type FGF21 activity (e.g., the ability to induce FGF21-likesignaling) using a suitable FGF21 reporter assay. The disclosed FGF21reporter assay measures activation of FGFR signaling via a MAPK pathwayreadout. β-Klotho is a co-receptor for FGF21 signaling, and although itis believed not to have any inherent signaling capability due to itsvery short cytoplasmic domain, it is required for FGF21 to inducesignaling through FGFRs.

Example 4.1 ELK-Luciferase Reporter Assay

ELK-luciferase assays were performed using a recombinant human 293Tkidney cell or CHO cell system. Specifically, the host cells wereengineered to over-express β-Klotho and luciferase reporter constructs.The reporter constructs contain sequences encoding GAL4-ELK1 and5×UAS-Luc, a luciferase reporter driven by a promoter containing fivetandem copies of the Gal4 binding site. Activation of the FGF21 receptorcomplex in these recombinant reporter cell lines induces intracellularsignal transduction, which in turn leads to ERK and ELK phosphorylation.Luciferase activity is regulated by the level of phosphorylated ELK, andis used to indirectly monitor and quantify FGF21 activity.

In one example, CHO cells were transfected sequentially using theLipofectamine 2000 transfection reagent (Invitrogen) according to themanufacturer's protocol with the receptor constructs expressingβ-Klotho, FGFR1c and the reporter plasmids: 5×Gal4-Luciferase (minimalTK promoter with 5×Gal4 binding sites upstream of luciferase) andGal4-ELK1. Gal4-ELK1 binds to the Gal4 binding sites and activatestranscription when it is phosphorylated by ERK. Luciferasetranscription, and thereby the corresponding enzymatic activity in thiscontext is regulated by the level of phosphorylated ELK1, and is used toindirectly monitor and quantify FGF21 activity.

Clone 16 was selected as the FGF21 luciferase reporter cell line basedon the optimal assay window of 10-20 fold with native FGF21 exhibitingan EC50 in the single nM range.

For the assay, the ELK-luciferase reporter cells were plated in 96 wellassay plates, and serum starved overnight. FGF21 or test samples wereadded for 6 hours at 37 degrees. The plates were then allowed to cool toroom temperature and the luciferase activity in the cell lysates wasmeasured with Bright-Glo (Promega).

Example 4.2 ERK-Phosphorylation Assay

Alternative host cell lines specifically L6 (a rat myoblastic cell line)was developed and applied to identify antibodies with FGF21-likesignaling activity. The rat L6 cell line is a desirable host cell linefor the activity assay because it is known to express minimal levels ofendogeneous FGF receptors. The L6 cells do not respond to FGF21 evenwhen transfected with β-Klotho expression vector and therefore providesa cleaner background. (Kurosu et al., (2007) J. Biol. Chem. 282,26687-26695).

Human primary preadipocytes isolated from subcutaneous adipose tissuesof multiple healthy nondiabetic donors were purchased from Zen-Bio, Inc.The preadipocytes were plated in 24-well plates and differentiated for18 days into mature adipocytes. After a 3-hour starvation period,adipocytes were treated with different concentrations of test moleculesfor 10 minutes. Following treatment, the media was aspirated and cellswere snap-frozen in liquid nitrogen. Cell lysates were prepared and ERKphosphorylation was measured using the Phospho-ERK1/2(Thr202/Tyr204;Thr185/Tyr187)/Total ERK1/2 Assay Whole Cell Lysate Kit from Meso ScaleDiscovery.”

L6 cells were maintained in Dulbecco's modified Eagle's mediumsupplemented with 10% fetal bovine serum and penicillin/streptomycin.Cells were transfected with plasmids expressing β-Klotho and individualFGFR using the Lipofectamine 2000 transfection reagent (Invitrogen)according to the manufacturer's protocol.

Analysis of FGF signaling in L6 cells was performed as described in theliterature (Kurosu et al., (2007) J. Biol. Chem. 282, 26687-26695). Cellcultures were collected 10 min after the treatment of FGF21 or testmolecules and snap frozen in liquid nitrogen, homogenized in the lysisbuffer and ERK phosphorylation was measured using thePhospho-ERK1/2(Thr202/Tyr204; Thr185/Tyr187)/Total ERK1/2 Assay WholeCell Lysate Kit from Meso Scale Discovery.”

In addition, the factor-dependent mouse BaF3 cell-based proliferationassay used frequently for cytokine receptors can also be developed andapplied.

Among the hybridoma supernatants tested in the CHO cell (Clone 16) basedhuman FGF21 ELK-luciferase reporter assay, over 140 were identified aspositive (>20% of the activity of FGF21) when compared to 20 nM FGF21 asthe positive control (FIGS. 3 and 4).

Antibodies can be purified from the conditioned media of the hybridomacultures of these positives and tested again in the CHO cell basedELK-luciferase reporter assay to assess the potency of therepresentative antibodies in the dose-responsive assay and determine theEC50. The activities and potency can be confirmed in the L6 cell basedERK1/2-phosphrylation assay. The EC50 is expected to be consistent tothe ELK-luciferase assay in the CHO stable cell line Clone 16.

Example 5 Determining that Induction of FGF21-Like Signaling is Specificto the FGFR/13Klotho Complex

FGF21 has been reported to signal through multiple receptor complexesincluding FGFR1c, 2c, 3c, and 4 when paired with β-Klotho. Theselectivity of the FGF21 agonistic antibodies can be determined in therat myoblastic L6 cells transfected with vectors expressing therespective FGFRs and β-Klotho as described in Example 4.2.

Observed selectivity would be strongly suggestive that the action ofthese antibodies is β-Klotho-dependent yet it must also involve the FGFRcomponent of the signaling complex. The results are set forth in Table 6below.

TABLE 9 FGFR Selectivity Molecule FGFR1c FGFR2c FGFR3c FGFR4 Fgf21 + + +− FGF19 + + + + 16H7 D58A + − − − 49H12.1 + − − − 51A8.1 + − − −51E5.1 + − − − 54A1.1 + − − − 60D7.1 + − − − 63A10.1 + − − − 64B10.1 + −− − 65C3.1 + − − − 66G2.1 + − − − 67F5.1 + − − − 67C10.1 + − − −68C8.1 + − − − 49C8.1 + − − − 49G3.3 + − − − 56E7.3 + − − − 52A8.1 + − −−

Example 5.1 Binding Specificity is Exclusively β-Klotho Dependent

The binding specificity of the reporter assay positive antibodies in thehybridoma supernatants was determined by FACS using 293T cellstransiently transfected to express full length FGFR1c alone, β-Klothoalone or FGFR1c and β-Klotho together. Over 98% (141 out of 143hybridomas) bind β-Klotho alone whereas none bind FGFR1c alone.

Example 6 Activity in Primary Human Adipocytes

FGF21 stimulates glucose uptake and lipolysis in cultured adipocytes,and adipocytes are considered to be more physiologically relevant thanthe recombinant reporter cell system.

A panel of the antibodies were tested in the human adipocyte assay forErk-phosphorylation activity as described in Example 4.2 and comparedwith FGF21 for their EC50. The results are set forth below in Table 10below.

TABLE 10 Activity of Antibodies on pERK Human Adipocyte Assay MoleculeEC₅₀ Fgf21 0.623 16H7 0.280 49H12.1 0.254 51A8.1 0.213 51E5.1 3.22154A1.1 0.206 60D7.1 0.496 63A10.1 0.435 64B10.1 0.955 65C3.1 6.38766G2.1 3.529 67F5.1 1.438 67C10.1 5.789 68C8.1 1.216 49C8.1 0.243 49G3.31.424 56E7.3 0.916 58C2.1 0.317

Example 7 Competition Binding and Epitope Binning

To compare the similarity of the binding sites of the antibodies on theFGF21 receptor, a series of competition binding experiments can beperformed and measured by Biacore. In one example, representativeagonistic FGF21 receptor antibodies (and any controls) can beimmobilized on the sensor chip surface. Soluble human FGFR1c/β-KlothoECD-Fc complex or β-Klotho can then be captured on the immobilizedantibody surfaces. Finally, several of the test FGF21 receptorantibodies can be injected individually over the captured soluble humanFGF21 receptor or β-Klotho. If the injected antibody recognizes adistinct binding site relative to that recognized by the immobilizedantibody, a second binding event will be observed. If the antibodiesrecognize very similar binding site, no more binding will be observed.

Alternatively or additionally, a Biacore analysis can be carried outwith biotinylated-FGF21 immobilized on the sensor ship. 10 nM solubleβ-Klotho is then passed over the chip alone or mixed with the individualtest antibodies at 100 nM. The results are set forth below in Table 11below.

TABLE 11 Epitope Binning Summary Bin 1: 2 ^(nd) Campaign - 24H11, 17C3,16H7, 20D4, 21B4, 22H5, 23F8, 21H2, 18B11; 3 ^(rd) Campaign - 40D2,46D11 Current - 49H12, 51A8, 54A1, 60D7, 49C8, 49G3, 56E7, 63A10, 64B10(64B10.1), 67C8, 68C8.1 Bin 2: 2 ^(nd) Campaign - 17D8, 12C11, 26H11,12E4, 18G1; 3 ^(rd) Campaign - 37D3 Bin 3: 3 ^(rd) Campaign - 39F7,38F2, 39F11, 39G5 Bin 4: 3 ^(rd) Campaign - 20E8 Bin 5: current - 51E5Bin 6: current - 52A8 (52A8.1), 67F5 (67F5.1), 67C10 (67C10.1), 65C3.1,66G2.1 Bold samples in bold are recombinant mAbs Italicized samples arefrom hybridoma supernatants.

Example 8 Recognition of Native and Denatured Structures

The ability of disclosed antigen binding proteins to recognize denaturedand native structures was investigated. The procedure and results wereas follows.

Example 8.1 FGF21 Receptor Agonistic Antibodies do not RecognizeDenatured Structures

Cell lysates from CHO cells stably expressing FGF21 receptor (FGFR1c andβ-Klotho) or CHO parental cells were diluted with sample buffer withoutbeta-mercaptoethanol (non-reducing conditions). 20 μl of cell lysatewere loaded per lane on adjacent lanes separated with a molecular weightmarker lane on 4-20% SDS-PAGE gels. Following electrophoresis, the gelswere blotted onto 0.2μ nitrocellulose filters. The blots were treatedwith Tris-buffered saline/Triton-X (TBST) plus 5% non-fat milk (blockingbuffer) for 30 minutes. The blots were then cut along the molecularweight marker lanes. The strips were probed with commercial goatanti-murine βKlotho or mouse anti-huFGFR1 (R&D Diagnostics) in TBST/5%milk. Blots were incubated with the antibodies for one hour at roomtemperature, followed by three washes with TBST+1% milk. The blots werethen probed with anti-human or anti-goat IgG-HRP secondary antibodiesfor 20 min. Blots were given three 15 minute washes with TBST followedby treatment with Pierce Supersignal West Dura developing reagent (1minute) and exposure to Kodak Biomax X-ray film.

The commercial anti-β-Klotho and anti-FGFR1 antibodies detected thecorresponding receptor proteins in the SDS-PAGE indicating they bind todenatured receptor proteins.

Example 8.2

FGF21 Receptor Agonistic Antibodies Bind to Native Receptor Structure

A FACS binding assay was performed with several commercially availableFGFR1c and β-Klotho antibodies, and several of the disclosed FGF21receptor agonistic antibodies. The experiments were performed asfollows.

CHO cells stably expressing FGF21 receptor were treated with R&D Systemsmouse anti-huFGFR1, goat anti-mu β-Klotho (1 μg per 1×10⁶ cells in 100μl PBS/0.5% BSA). Cells were incubated with the antibodies at 4° C.followed by two washes with PBS/BSA. Cells were then treated withFITC-labeled secondary antibodies at 4° C. followed by two washes. Thecells were resuspended in 1 ml PBS/BSA and antibody binding was analyzedusing a FACSCalibur™ instrument.

None of the commercial anti-β-Klotho or anti-FGFR1 antibodies testedbind well to cell surface FGF21 receptor, as determined by FACS. Thisobservation further confirmed that the commercial antibodies to thereceptor components bind to denatured and non-native structure whereasall of the agonistic antibodies described herein bind receptors on cellsurface as shown by FACS or FMAT which were the initial screens.

Example 9 Arginine Scanning

As described above, antigen binding proteins that bind a complexcomprising b-Klotho and one of FGFR1c, FGFR2c and FGFR3c can be createdand characterized. To determine the neutralizing determinants on humanFGFR1c and/or β-Klotho that these various antigen binding proteinsbound, a number of mutant FGFR1c and/or β-Klotho proteins can beconstructed having arginine substitutions at select amino acid residuesof human FGFR1c and/or β-Klotho. Arginine scanning is an art-recognizedmethod of evaluating where antibodies, or other proteins, bind toanother protein, see, e.g., Nanevicz et al., (1995) J. Biol. Chem.,270:37, 21619-25 and Zupnick et al., (2006) J. Biol. Chem., 281:29,20464-73. In general, the arginine sidechain is positively charged andrelatively bulky as compared to other amino acids, which can disruptantibody binding to a region of the antigen where the mutation isintroduced. Arginine scanning is a method that determines if a residueis part of a neutralizing determinant and/or an epitope.

Various amino acids distributed throughout the human FGFR1c and/orβ-Klotho extracellular domains can be selected for mutation to arginine.The selection can be biased towards charged or polar amino acids tomaximize the possibility of the residue being on the surface and reducethe likelihood of the mutation resulting in misfolded protein. Usingstandard techniques known in the art, sense and anti-senseoligonucleotides containing the mutated residues can be designed basedon criteria provided by Stratagene Quickchange® II protocol kit(Stratagene/Agilent, Santa Clara, Calif.). Mutagenesis of the wild-type(WT) FGFR1c and/or β-Klotho sequences can be performed using aQuickchange® II kit (Stratagene). Chimeric constructs can be engineeredto encode a FLAG-histidine tag (six histidines (SEQ ID NO: 1830)) on thecarboxy terminus of the extracellular domain to facilitate purificationvia the poly-His tag.

Multiplex analysis using the Bio-Plex Workstation and software (BioRad,Hercules, Calif.) can be performed to determine neutralizingdeterminants on human FGFR1c and/or β-Klotho by analyzing exemplaryhuman FGFR1c and/or β-Klotho mAbs differential binding to argininemutants versus wild-type FGFR1c and/or β-Klotho proteins. Any number ofbead codes of pentaHis-coated beads (“penta-His” disclosed as SEQ ID NO:1831) (Qiagen, Valencia, Calif.) can be used to capture histidine-taggedprotein. The bead codes can allow the multiplexing of FGFR1c and/orβ-Klotho arginine mutants and wild-type human FGFR1c and/or β-Klotho.

To prepare the beads, 100 ul of wild-type FGFR1c and/or β-Klotho andFGFR1c and/or β-Klotho arginine mutant supernatants from transientexpression culture are bound to penta-His-coated beads (“penta-His”disclosed as SEQ ID NO: 1831) overnight at 4° C. or 2 hours at roomtemperature with vigorous shaking. The beads are then washed as per themanufacturer's protocol and the bead set pooled and aliquoted into 2 or3 columns of a 96-well filter plate (Millipore, Billerica, Mass.,product #MSBVN1250) for duplicate or triplicate assay points,respectively. 100 μl anti-FGFR1c and/or anti-β-Klotho antibodies in4-fold dilutions are added to the wells, incubated for 1 hour at roomtemperature, and washed. 100 μl of a 1:100 dilution of PE-conjugatedanti-human IgG Fc (Jackson Labs., Bar Harbor, Me.) is added to eachwell, incubated for 1 hour at room temperature and washed. Beads areresuspended in 1% BSA, shaken for 3 minutes, and read on the Bio-Plexworkstation. Antibody binding to FGFR1c and/or β-Klotho arginine mutantprotein is compared to antibody binding to the human FGFR1c and/orβ-Klotho wild-type from the same pool. A titration of antibody overapproximately a 5 log scale can be performed. Median FluorescenceIntensity (MFI) of FGFR1c and/or β-Klotho arginine mutant proteins canbe graphed as a percent of maximum wild-type human FGFR1c and/orβ-Klotho signal. Those mutants for which signal from all the antibodiesare below a cut-off value, e.g., 30% of wild-type FGFR1c and/or β-Klothocan be deemed to be either of too low a protein concentration on thebead due to poor expression in the transient culture or possiblymisfolded and can be excluded from analysis. Mutations (i.e., argininesubstitutions) that increase the EC50 for the FGFR1c and/or β-Klotho mAbby a cut-off value, e.g., 3-fold or greater (as calculated by, e.g.,GraphPad Prism®) can be considered to have negatively affected FGFR1cand/or β-Klotho mAb binding. Through these methods, neutralizingdeterminants and epitopes for various FGFR1c and/or β-Klotho antibodiesare elucidated.

Example 10 Protease Protection Analysis

Regions of the human FGF21 receptor bound by the antigen bindingproteins that bind human FGF21 receptor, e.g., FGFR1c, β-Klotho orFGFR1c and β-Klotho complex can be identified by fragmenting human FGF21receptor into peptides with specific proteases, e.g., AspN, Lys-C,chymotrypsin or trypsin. The sequence of the resulting human FGF21receptor peptides (i.e., both disulfide- and non-disulfide-containingpeptide fragments from FGFR1c and β-Klotho portions) can then bedetermined. In one example, soluble forms of a human FGF21 receptor,e.g., a complex comprising the FGFR1c ECD-Fc and β-Klotho ECD-Fcheterodimer described herein can be digested with AspN (which cleavesafter aspartic acid and some glutamic acid residues at the amino end) byincubating about 100 μg of soluble FGF21 receptor at 1.0 mg/ml in 0.1Msodium phosphate (pH 6.5) for 20 hrs at 37° C. with 2 μg of AspN.

A peptide profile of the AspN digests can then be generated on HPLCchromatography while a control digestion with a similar amount ofantibody is expected to be essentially resistant to AspN endoprotease. Aprotease protection assay can then be performed to determine theproteolytic digestion of human FGF21 receptor in the presence of theantigen binding proteins. The general principle of this assay is thatbinding of an antigen binding protein to the FGF21 receptor can resultin protection of certain specific protease cleavage sites and thisinformation can be used to determine the region or portion of FGF21receptor where the antigen binding protein binds.

Briefly, the peptide digests can be subjected to HPLC peptide mapping;the individual peaks are collected, and the peptides are identified andmapped by on-line electrospray ionization LC-MS (ESI-LC-MS) analysesand/or by N-terminal sequencing. HPLC analyses for these studies can beperformed using a narrow bore reverse-phase C18 column (AgilentTechnologies) for off-line analysis and using a capillary reverse phaseC18 column (The Separation Group) for LC-MS. HPLC peptide mapping can beperformed with a linear gradient from 0.05% trifluoroacetic acid (mobilephase A) to 90% acetonitrile in 0.05% trifluoroacetic acid. Columns canbe developed at desirable flow rate for narrow bore HPLC for off-line oron-line LC-MS analyses, and for capillary HPLC for on-line LC-MSanalyses.

Sequence analyses can be conducted by on-line LC-MS/MS and by Edmansequencing on the peptide peaks recovered from HPLC. On-line ESI LC-MSanalyses of the peptide digest can be performed to determine the precisemass and sequence of the peptides that are separated by HPLC. Theidentities of selected peptides present in the peptide peaks from theprotease digestion can thus be determined.

Example 11 Construction of Chimeric Receptors

An additional method of determining activation determinants on whichthese various antigen binding proteins bind is as follows. Specificchimeric FGFR1c and/or β-Klotho proteins between human and mouse speciescan be constructed, expressed in transient or stable 293 or CHO cells(as described herein) and tested. For example, a chimeric FGF21 receptorcan be constructed comprising native human FGFR1c, FGFR2c, FGFR3c orFGFR4 receptors. By way of example, FGFR1c can be paired with chimerichuman/mouse β-Klotho in which selected regions or sequences on the humanβ-Klotho are systematically replaced by the corresponding mouse-specificresidues (see, e.g., FIG. 2A-2C). Similarly, native human β-Klotho canbe paired with chimeric human/mouse FGFR1c, FGFR2c, FGFR3c or FGFR4.Here, selected regions or sequences on the human FGFR1c aresystematically replaced by the corresponding mouse-specific residues(see, e.g., the alignments of FIGS. 1A-1B). The critical sequencesinvolved in the binding and/or activity of the antigen binding proteinscan be derived through binding assay or activity measurements describedin previous Examples 4, 5, 6, and 7 based on the chimeric FGF21receptors.

Example 11.1 Construction of Specific Chimeras

Human-mouse β-Klotho chimeras were constructed using the methodologydescribed above. A schematic of the chimeras constructed is presented inFIG. 4. In summary, the chimeras generated comprised (from N- toC-terminus) a fusion of a human β-Klotho sequence fused to a murineβ-Klotho sequence fused to a human β-Klotho sequence. Human β-KlothoKlotho (SEQ ID NO: 7) was used as a framework into which regions ofmurine β-Klotho (full length sequence shown in SEQ ID NO:468) wereinserted. The regions of murine β-Klotho that were inserted were asfollows:

Murine Residues 82P-520P (amino acids 82 to 520 of SEQ ID NO: 10)PKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDMKGRFP Murine Residues 506F-1043S(amino acids 506 to 1043 of SEQ ID NO: 10)FPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQFYSKLISSSGLPAENRSPACGQPAEDTDCTICSFLVEKKPLIFFGCCFISTLAVLLSITVFHHQKRRKFQKARNLQNIPLKKGHSRVFS Murine Residues 1M-193L (aminoacids 506 to 1043 of SEQ NO: 10)MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAVTGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTL Murine Residues 82P-302S(amino acids 82 to 302 of SEQ ID NO: 10)PKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVW HNYDKNFRPHQKGWLSITLGSMurine Residues 194Y-416G (amino acids 194 to 416 of SEQ ID NO: 10)YHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENG Murine Residues 302S-506F (amino acids 302 to506 of SEQ ID NO: 10) SHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQII QDNGF Murine Residues416G-519P (amino acids 416 to 519 of SEQ ID NO: 10)GWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDM KGRF Murine Residues507P-632G (amino acids 507 to 632 of SEQ NO: 10)PLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLG Murine Residues 520P-735A (amino acids 520 to735 of SEQ ID NO: 10) PCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQ VWHLYDRQYRPVQHGAMurine Residues 632G-849Q (amino acids 632 to 849 of SEQ ID NO: 10)GVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIH KQLNTNRSVADRDVQFLQMurine Residues 735A-963S (amino acids 735 to 963 of SEQ ID NO: 10)AVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQFYSKLISSS Murine Residues 1M-81F (amino acids 1 to81 of SEQ ID NO: 10) MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAVTGFSGDGKAIWDKKQYVSPVNPSQLFLYDTF Murine Residues 82P-193L (amino acids 82to 193 of SEQ ID NO: 10)PKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDS LVLRNIEPIVTL

The chimeras that were generated using the murine β-Klotho sequencescomprised the following:

TABLE 12 N-terminal C-terminal SEQ. Human β- Mouse β- Human β- Con-Construct ID Klotho Klotho Klotho struct Identifier NO. ResiduesResidues Residues 1 huBeta_Klotho (1- 1-81   82-520 523-1044 81,523-1044) (muBetaKLOTHO 82-520) 2 huBeta_Klotho (1- 1-507  506-1043 507)(muBetaKLOTHO 506F-1045S) 3 huBeta_Klotho  1-193 194-1044 (194-1044)(muBetaKLOTHO 1-L193) 4 huBeta_Klotho (1- 1-81   82-302 303-1044 81,303-1044) (muBetaKLOTHO 82P-302S) 5 huBeta_Klotho (1- 1-193 194-416419-1044 193, 419-1044) (muBetaKLOTHO Y194-416G) 6 huBeta_Klotho(1-1-301 302-506 509-1044 301, 509-1044) (muBetaKLOTHO S302-F506) 7huBeta_Klotho(1- 1-417 416-519 522-1044 417, 522-1044) (muBetaKLOTHOG416-F519) 8 huBeta_Klotho (1- 1-508 507-632 635-1044 507, 635-1044)(muBeta KLOTHO F06-G632) 9 huBeta_Klotho (1- 1-521 520-735 738-1044 521,738-1044) (muBeta KLOTHO 520P-735A) 10 huBeta_Klotho (1- 1-633 632-849852-1044 633, 852-1044) (muBeta KLOTHO 632G-849Q) 11 huBeta_Klotho (1-1-736 735-963 967-1044 736, 967-1044) (muBeta KLOTHO 735A-963S) 12huBeta_Klotho  1-81  82-1044 (82-1044) (muBeta KLOTHO 1-81F) 13huBeta_Klotho (1- 1-81   82-193 194-1044 81, 194-1044) (muBeta KLOTHO82P-193L) 14 huBeta_Klotho (1- 1-301  302-506, 967-1044 301, 509-743,967- 742-964 1044) (muBeta KLOTHO 302- 506, 742-964)The generated chimeras comprised the following amino acid sequences:

(i) huBeta_Klotho(1-81, 523-1044)(muBetaKLOTHO 82-520) (SEQ ID NO: 1898)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDMKGRFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (ii)huBeta_Klotho(1-507)(muBetaKLOTHO 506F-1045S) (SEQ ID NO: 1899)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQFYSKLISSSGLPAENRSPACGQPAEDTDCTICSFLVEKKPLIFFGCCFISTLAVLLSITVFHHQKRRKFQKARNLQNIPLKKGHSRVFS (iii)huBeta_Klotho(194-1044)(muBetaKLOTHO 1-L193) (SEQ ID NO: 1900)MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAVTGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (iv) huBeta_Klotho(1-81,303-1044)(muBetaKLOTHO 82P-302S) (SEQ ID NO: 1901)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (v) huBeta_Klotho(1-193,419-1044)(muBetaKLOTHO Y194-416G) (SEQ ID NO: 1902)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (vi) huBeta_Klotho(1-301,509-1044)(muBetaKLOTHO S302-F506) (SEQ ID NO: 1903)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (vii) huBeta_Klotho(1-417,522-1044)(muBetaKLOTHO G416-F519) (SEQ ID NO: 1904)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDMKGRFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (viii) huBeta_Klotho(1-507,635-1044)(muBeta KLOTHO F06-G632) (SEQ ID NO: 1905)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (ix) huBeta_Klotho(1-521,738-1044)(muBeta KLOTHO 520P-735A) (SEQ ID NO: 1906)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (x) huBeta_Klotho(1-633,852-1044)(muBeta KLOTHO 632G-849Q) (SEQ ID NO: 1907)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (xi) huBeta_Klotho(1-736,967-1044)(muBeta KLOTHO 735A-963S) (SEQ ID NO: 1908)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQFYSKLISSSGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (xii)huBeta_Klotho(82-1044)(muBeta KLOTHO 1-81F) (SEQ ID NO: 1909)MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAVTGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (xiii) huBeta_Klotho(1-81,194-1044)(muBeta KLOTHO 82P-193L) (SEQ ID NO: 1910)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS (xiv) huBeta_Klotho (1-301,509-743, 967-1044) (muBetaKLOTHO 302-506, 742-964) (SEQ ID NO: 1911)MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAVTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQFYSKLISSSGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

Various antigen binding proteins provided herein, as well as humanFGF21, were tested for the ability to activate chimeras in L6 cells.FIG. 5 shows the observed results with each tested molecule.

These data indicate that while human FGF21 was able to activate FGFR1ccombined with all of the human/mouse β-Klotho chimeras (the “+” signindicates activity on the receptor), the substitutions of mousesequences into human β-Klotho affected the activities of 16H7, 37D3, and39F7 (See FIG. 5). These results suggest that β-Klotho sequences 1-81,302-522, and 849-1044 are important for the activities of agonisticantigen binding proteins and may represent an important epitope fortheir function.

In addition, various antigen binding proteins were also tested forbinding to the various human/mouse β-Klotho chimeras transientlyexpressed on the surface of HEK-293T cells by flow cytometry.Transfection and flow-cytometry was performed as described in Example12. It will be appreciated that antibodies which do not have the abilityto cross-bind full length murine β-Klotho are unable to bind thehuman/mouse β-Klotho chimera if the chimera spans a region of theantibody's binding site. In this manner, the binding profile of eachantibody on the panel of chimeras reveals epitope information for theantibody. Data is shown below in Table 10. The anti-β-Klotho antibody2G10 (which binds both human and mouse β-Klotho) was used as thepositive control for expression of each human/mouse chimera. Using thispositive control it was determine the expression level of chimeras 7 and8 were not high enough to provide robust data and therefore they wereeliminated from the analysis. One antibody, 26H11, was found to bind tofull-length mouse β-Klotho and therefore could not be assigned anepitope in this analysis. Other antibodies which did not cross-bind tomouse β-Klotho could be group into epitope clusters. The first clusterincluded antibodies 16H7, 46D11, and 49G3.3, which antibodies did notbind to chimera #3 and chimera #12, indicating that the epitope includesthe 1-81 region. Additionally, this group of antibodies also lackedobserved binding to chimeras 1, 5, 6 and 14, which indicates that theepitope also includes the 294-506 region. Taken together, this datasuggests that these antibodies have a complex non-linear type ofepitope.

A second cluster included only antibody 65C3.1. This antibody lackedbinding to chimeras #2, #11, and #14, indicating an epitope in theregion of 849-936. A third cluster, including antibodies 49H12.1,54A1.1, 49C8.1, 51A8.1, 63A10.1, 64B10.1, 68C8.1 and 39F7, lackedbinding to chimera #1, #5, and #6, indicating that their epitope is inthe 302-416 region. The forth cluster included antibodies 67C10.1,51E5.1, 52A8.1, 66G2, 167F5.1, which lacked binding on chimeras #2, #8,#9, #10, #11, and #14 indicating that the epitope for these antibodieslies within region 506-1045. A “+” or “−” symbol in the chart belowindicates binding of the respective antibody (“+”), or lack of binding(“−”) to the chimera and/or the respective ortholog of β-Klotho, or MockCells (negative control).

TABLE 13 Chimera Binding Mock cells CHIMERA # hu β- mu β- (Neg. Epitope1 2 3 4 5 6 9 10 11 12 13 14 Klotho klotho Cont.) Region2G10 + + + + + + + + + + + + + + − 26H11 + + + + + + + + + + + + + + −16H7 − + − + − − + + + − + − + − − 1-81 & 49G3.3 − + − + − − + + + − +− + − − 302-416 46D11 − + − + − − + + + − + − + − − 49H12.1 − + + + −− + + + + + − + − − 302-416 54A1.1 − + + + − − + + + + + − + − − 49C8.1− + + + − − + + + + + − + − − 51A8.1 − + + + − − + + + + + − + − −63A10.1 − + + + − − + + + + + − + − − 64B10.1 − + + + − − + + + + + − +− − 68C8.1 − + + + − − + + + + + − + − − 39F7 − + + + − − + + + + + − +− − 65C3.1 + − + + + + + + − + + − + − − 849-936 67C10.1 + − + + + + − −− + + − + − −  506-1045 51E5.1 + − + + + + − − − + + − + − − 52A8.1 +− + + + + − − − + + − + − − 66G2.1 + − + + + + − − − + + − + − −67F5.1 + − + + + + − − − + + − + − − IgG2/K − − − − − − − − − − − − − −− Control IgG4/K − − − − − − − − − − − − − − − Control Secondary − − − −− − − − − − − − − − − Only

Example 12 FGF21 Receptor Agonistic Antibodies Binding Selectivity

A panel of FGF21 receptor agonistic antibodies were assayed using flowcytometry for the binding to human FGFR1/human β-klotho transientlyco-transfected HEK293T cells, human FGFR1c transiently transfectedHEK293T cells and β-klotho transiently transfected HEK293T cells. Inaddition, binding was also tested on HEK-293T cells transientlytransfected with cynomologous monkey orthologs of FGFR1c and β-klotho.Cells were transfected by preparing bug plasmid DNA in 500 ul OptiMEM™media (Invitrogen™) and mixing this with 10 ul of 293fectin™ in 500 ulOptiMEM™ media, and then incubating the solution for 5 minutes at roomtemperature. This solution was then added dropwise to 10 million HEK293Tcells in 10 ml of media. 24 hours following transfection, the cells werewashed and 50,000 cells were stained with each primary antibody, 50 ulof unpurified hybridoma supernatant was diluted 1:2 and used forstaining cells. After a one hour incubation at 4° c., the cells werewashed and an anti-Human Fc-specific secondary was added. Stained cellswere then analyzed on a flow cytometer. The panel of hybridomasupernatants tested all bound specifically to human β-Klotho/humanFGFR1c co-transfected cells as well as human β-Klotho transfected alone.Data is shown below in Table 11. No staining was detected for any of theantibodies on cells transfected with FGFR1c alone. All antibodies except64B10.1 and 68C8.1 specifically detected cynomologousβ-Klotho/cynoFGFR1c co-transfected cells.

TABLE 14 FGFR Antibody Selectivity Human Human β- HuFGFR1c/Hu Cyno MockFGFR1c Klotho β-Klotho Co- FGFR1c/Cyno Transfected Transfect Tranfectedtransfected β-Klotho Co- 293T cells 293T cells 293T Cells 293T Cellstransfected Cells Antibody GeoMean GeoMean GeoMean GeoMean GeoMean49G3.3 648 706 14891 17919 25947 49H12.1 581 719 16213 21731 2087051E5.1 723 747 16900 20951 36536 51A8.1 728 795 17799 22826 18476 54A1.1709 770 14317 18701 11106 59G10.3 686 780 15669 21105 33464 63A10.1 648834 17442 20432 32558 64B10.1 624 691 14939 19850 701 65C3.1 705 71913720 18835 24564 66G2.1 695 780 12671 16715 21566 67F5.1 632 757 1348213948 15784 67C10.1 688 780 15114 18896 4063 68C8.1 592 798 15905 20622750 16H7 @ 723 869 16335 20686 31319 5 ug/ml

Example 13 Hotspot/Covariant Mutants

A total of 17 antibodies were analyzed for potential hotspots andcovariance violations. The designed variants (shown below) outline aminoacid substitutions capable of reducing and/or avoiding isomerization,deamidation, oxidation, covariance violations, and the like. In the databelow, “02 49C8.1_VK: [F21I]” refers to a variant of the parentalantibody 49C8.1 that has a mutation at position 21, from F (Phe) to I(Isoleucine). Note that a structure-based numbering scheme is followedfor designating amino acid positions. It will be appreciated that thesesingle point mutations can be combined in any combinatorial manner inorder to arrive at a final desired molecule. The data are shown below inTable 15 and Table 16.

TABLE 15 Antibody 49C8.1 02 49C8.1_VK: [F21I] 03 49C8.1_VK: [F91L] 0449C8.1_VK: [I101F] 05 49C8.1_VK: [I101V] 06 49C8.1_VK: [P141Q] 0749C8.1_VK: [P141G] 08 49C8.1_VH: [T48P] 09 49C8.1_VH: [N61Q] 1049C8.1_VH: [G65T] Antibody 49H12_N83D 01 49H12_N83D_VK: [F91L] 0249H12_N83D_VK: [I101F] 03 49H12_N83D_VK: [I101V] 04 49H12_N83D_VH:[M24K] 05 49H12_N83D_VH: [I30T] 06 49H12_N83D_VH: [T48P] 0749H12_N83D_VH: [W57Y] 08 49H12_N83D_VH: [W111Y] Antibody 49G3.3 0149G3.3_VK: [F91L] 02 49G3.3_VK: [I101F] 03 49G3.3_VK: [I101V] 0449G3.3_VK: [G141Q] 05 49G3.3_VH: [E17Q] 06 49G3.3_VH: [V25F] 0749G3.3_VH: [T56A] 08 49G3.3_VH: [T56G] 09 49G3.3_VH: [T144L] 1049G3.3_VH: [T144M] Antibody 51A8.1 01 51A8.1_VL: [I98T] 02 51A8.1_VL:[I98A] 03 51A8.1_VH: [R17G] 04 51A8.1_VH: [D61E] 05 51A8.1_VH: [D72E] 0651A8.1_VH: [D110E] Antibody 51E5.1 01 51E5.1_VK: [N53K] 02 51E5.1_VK:[R54L] 03 51E5.1_VK: [R54S] 04 51E5.1_VK: [G141Q] 05 51E5.1_VH: [D59E]06 51E5.1_VH: [H60T] Antibody 52A8.1 01 52A8.1_VK: [F10S] 02 52A8.1_VK:[H44Y] 03 52A8.1_VK: [H44F] 04 52A8.1_VK: [G141Q] 05 52A8.1_VH: [W57Y]06 52A8.1_VH: [R95S] 07 52A8.1_VH: [W135Y] Antibody 54A1.1_N83D 0154A1.1_N83D_VK: [A5T] 02 54A1.1_N83D_VK: [L46Q] 03 54A1.1_N83D_VK:[G81S] 04 54A1.1_N83D_VK: [F91L] 05 54A1.1_N83D_VK: [I101F] 0654A1.1_N83D_VK: [I101V] 07 54A1.1_N83D_VK: [P141G] 08 54A1.1_N83D_VK:[P141Q] 09 54A1.1_N83D_VH: [T48P] 10 54A1.1_N83D_VH: [W57Y] 1154A1.1_N83D_VH: [W111Y] Antibody 56E7.3 01 56E7.3_VK: [N53K] 0256E7.3_VK: [F91L] 03 56E7.3_VK: [I101F] 04 56E7.3_VK: [P141Q] 0556E7.3_VK: [P141G] 06 56E7.3_VK: [T144K] 07 56E7.3_VK: [T144R] 0856E7.3_VH: [L31F] 09 56E7.3_VH: [D65E] 10 56E7.3_VH: [T84K] 1156E7.3_VH: [R95S] Antibody 58C2.1 01 58C2.1_VK: [D36E] 02 58C2.1_VH:[R17G] 03 58C2.1_VH: [D61E] 04 58C2.1_VH: [D72E] 05 58C2.1_VH: [N116Q]Antibody 60D7.1_N30T 01 60D7.1_N30T_VK: [D33E] 02 60D7.1_N30T_VK: [D36E]03 60D7.1_N30T_VH: [R17G] 04 60D7.1_N30T_VH: [D61E] 05 60D7.1_N30T_VH:[D72E] 06 60D7.1_N30T_VH: [W115Y] Antibody 63A10.1_C58S 0163A10.1_C58S_VL: [H9L] 02 63A10.1_C58S_VL: [H9P] 03 63A10.1_C58S_VL:[T15L] 04 63A10.1_C58S_VL: [T15P] 05 63A10.1_C58S_VL: [A16G] 0663A10.1_C58S_VL: [M18T] 07 63A10.1_C58S_VL: [D51A] 08 63A10.1_C58S_VL:[D51S] 09 63A10.1_C58S_VL: [D51F] 10 63A10.1_C58S_VL: [D67E] 1163A10.1_C58S_VL: [P83S] 12 63A10.1_C58S_VL: [E97Q] 13 63A10.1_C58S_VL:[D110E] 14 63A10.1_C58S_VL: [D136E] 15 63A10.1_C58S_VH: [D11G] 1663A10.1_C58S_VH: [K14Q] 17 63A10.1_C58S_VH: [I29F] 18 63A10.1_C58S_VH:[G56S] 19 63A10.1_C58S_VH: [D64E] 20 63A10.1_C58S_VH: [G84D] 2163A10.1_C58S_VH: [G84N] 22 63A10.1_C58S_VH: [T98A] 23 63A10.1_C58S_VH:[T107A] 24 63A10.1_C58S_VH: [T108R] 25 63A10.1_C58S_VH: [D109E] 2663A10.1_C58S_VL: [W109Y] Antibody 63A10.3_N20R_C42S 0163A10.3_N20R_C42S_VL: [W109Y] 02 63A10.3_N20R_C42S_VL: [D67E] 0363A10.3_N20R_C42S_VL: [D110E] 04 63A10.3_N20R_C42S_VH: [D11G] 0563A10.3_N20R_C42S_VH: [K14Q] 06 63A10.3_N20R_C42S_VH: [I29F] 0763A10.3_N20R_C42S_VH: [G56S] 08 63A10.3_N20R_C42S_VH: [D64E] 0963A10.3_N20R_C42S_VH: [G84N] 10 63A10.3_N20R_C42S_VH: [T98A] 1163A10.3_N20R_C42S_VH: [T107A] 12 63A10.3_N20R_C42S_VH: [T108R] 1363A10.3_N20R_C42S_VH: [D109E] 14 63A10.3_N20R_C42S_VL: [W109Y] Antibody64B10.1 01 64B10.1_VL: [G92A] 02 64B10.1_VL: [G99E] 03 64B10.1_VL:[D110E] 04 64B10.1_VH: [L5Q] 05 64B10.1_VH: [T144L] 06 64B10.1_VH:[T144M] 07 64B10.1_VL: [W109Y] 08 64B10.1_VH: [W113Y] Antibody 66G2 0166G2_VK: [R54L] 02 66G2_VK: [K88E] 03 66G2_VK: [K88D] 04 66G2_VK:[N110Q] 05 66G2_VH: [R17G] 06 66G2_VH: [D61E] 07 66G2_VH: [D72E] 0866G2_VH: [I78F] 09 66G2_VH: [T108K] 10 66G2_VH: [T108R] Antibody 67F5 1.01 67F5_VK: [H57Y] 2. 02 67F5_VK: [Q97E] 3. 03 67F5_VK: [S98P] 4. 0467F5_VK: [A99E] 5. 05 67F5_VK: [N105Y] 6. 06 67F5_VH: [K5Q] 7. 0767F5_VK: [W135Y] 8. 08 67F5_VK: [W137Y] Antibody 67C10 1. 01 67C10_VK:[F2I] 2. 02 67C10_VK: [D36E] 3. 03 67C10_VH: [Q24K] 4. 04 67C10_VH:[D65E] Antibody 68C8 1. 01 68C8_VL: [G92A] 2. 02 68C8_VL: [G99E] 3. 0368C8_VL: [D110E] 4. 04 68C8_VH: [D29G] 5. 05 68C8_VH: [H83D] 6. 0668C8_VH: [G107A] 7. 07 68C8_VH: [T144L] 8. 08 68C8_VH: [T144M] 9. 0968C8_VL: [W109Y] 10. 10  68C8_VH: [W113Y]

TABLE 16 Exemplary Substitutions >49C8.1 VKDIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1912) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49H12 N83D VKDIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1914) >49H12 N83D VHQVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1915) >49G3.3 VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3 VHQVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1917) >51A8.1 VLNFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1918) >51A8.1 VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY GMDVWGQGTTVTVSS(SEQ ID NO: 1919) >51E5.1 VKDIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID NO:1920) >51E5.1 VHQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1921) >52A8.1 VKDIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1922) >52A8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1923) >54A1.1 N83D VKDIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1924) >54A1.1 N83D VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >56E7.3 VKDLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:1926) >56E7.3 VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >58C2.1 VKENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ ID NO:1928) >58C2.1 VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYPYYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 1929) >60D7.1 N30T VKDIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:1930) >60D7.1 N30T VHQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 1931) >63A10.1 C58S VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1 C58S VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.3 N20R C42S VLSYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKSGQSPVLVIYQDSERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTVLG (SEQ ID NO:1934) >63A10.3 N20R C42S VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1935) >64B10.1 VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1936) >64B10.1 VHQIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTTVTVSS (SEQID NO: 1937) >66G2 VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2 VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 1939) >67F5 VKENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:1940) >67F5 VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67C10 VKDFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ ID NO:1942) >67C10 VH EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW GQGTMVTVSS(SEQ ID NO: 1943) >68C8 VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8 VH QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 1945) >49C8.1 VK.02DIQMTQSPSSLSASVGDRVTITCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTLTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1946) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49C8.1 VK.03DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTLTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1947) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49C8.1 VK.04DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDFATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1948) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49C8.1 VK.05DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDVATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1949) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49C8.1 VK.06DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGQGTKVDLKR (SEQ ID NO:1950) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49C8.1 VK.07DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGGGTKVDLKR (SEQ ID NO:1951) >49C8.1 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1913) >49C8.1 VKDIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1912) >49C8.1 VH.08QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQAPGQGLEWMGWMNPNGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1952) >49C8.1 VKDIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1912) >49C8.1 VH.09QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPQGGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1953) >49C8.1 VKDIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID NO:1912) >49C8.1 VH.10TGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW GQGTLVTVSS (SEQID NO: 1954) >49H12 N83D VK.01DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTLTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1955) >49H12 N83D VHQVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1915) >49H12 N83D VK.02DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDFATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1956) >49H12 N83D VHQVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1915) >49H12 N83D VK.03DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDVATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1957) >49H12 N83D VHQVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1915) >49H12 N83D VKDIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1914) >49H12 N83D VH.04QVQLVQSGAEVKKPGASVKVSCKASGYIFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFWG QGTMVTVSS (SEQID NO: 1958) >49H12 N83D VKDIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1914) >49H12 N83D VH.05QVQLVQSGAEVKKPGASVKVSCMASGYTFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1959) >49H12 N83D VKDIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1914) >49H12 N83D VH.06QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQAPGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1960) >49H12 N83D VKDIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1914) >49H12 N83D VH.07QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGYMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFWG QGTMVTVSS (SEQID NO: 1961) >49H12 N83D VKDIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID NO:1914) >49H12 N83D VH.08QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPYSGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNYNYGAFDFW GQGTMVTVSS (SEQID NO: 1962) >49G3.3 VK.01DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1963) >49G3.3 VHQVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1917) >49G3.3 VK.02DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDFATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1964) >49G3.3 VHQVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1917) >49G3.3 VK.03DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDVATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1965) >49G3.3 VHQVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1917) >49G3.3 VK.04DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGQGTKVEIRR (SEQ ID NO:1966) >49G3.3 VHQVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1917) >49G3.3 VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3 VH.05QVTLKESGPVLVKPTQTLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1967) >49G3.3 VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3 VH.06QVTLKESGPVLVKPTETLTLTCTFSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1968) >49G3.3 VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3 VH.07QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLAHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1969) >49G3.3_VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3_VH.08QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLGHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTTVTVSS (SEQID NO: 1970) >49G3.3_VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3_VH.09QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTLVTVSS (SEQID NO: 1971) >49G3.3_VKDIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID NO:1916) >49G3.3_VH.10QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW GQGTMVTVSS (SEQID NO: 1972) >51A8.1_VL.01NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1973) >51A8.1_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY GMDVWGQGTTVTVSS(SEQ ID NO: 1919) >51A8.1_VL.02NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKAEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1974) >51A8.1_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY GMDVWGQGTTVTVSS(SEQ ID NO: 1919) >51A8.1_VLNFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1918) >51A8.1_VH.03QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY GMDVWGQGTTVTVSS(SEQ ID NO: 1975) >51A8.1_VLNFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1918) >51A8.1_VH.04QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYEGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYYG MDVWGQGTTVTVSS(SEQ ID NO: 1976) >51A8.1_VLNFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1918) >51A8.1_VH.05QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY GMDVWGQGTTVTVSS(SEQ ID NO: 1977) >51A8.1_VLNFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID NO:1918) >51A8.1_VH.06QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAEGDYPYYYYYY GMDVWGQGTTVTVSS(SEQ ID NO: 1978) >51E5.1_VK.01DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID NO:1979) >51E5.1_VHQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1921) >51E5.1_VK.02DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNLLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID NO:1980) >51E5.1_VHQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1921) >51E5.1_VK.03DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNSLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID NO:1981) >51E5.1_VHQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1921) >51E5.1_VK.04DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGQGTRVEIKR (SEQ ID NO:1982) >51E5.1_VHQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1921) >51E5.1_VKDIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID NO:1920) >51E5.1_VH.05QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELEHSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1983) >51E5.1_VKDIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID NO:1920) >51E5.1_VH.06QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDTSGSINYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT VSS (SEQ ID NO:1984) >52A8.1_VK.01DIQMTQSPSSLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1985) >52A8.1_VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1923) >52A8.1_VK.02DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1986) >52A8.1_VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1923) >52A8.1_VK.03DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWFQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1987) >52A8.1_VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1923) >52A8.1_VK.04DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR (SEQ ID NO:1988) >52A8.1_VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1923) >52A8.1_VKDIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1922) >52A8.1_VH.05QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGYINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1989) >52A8.1_VKDIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1922) >52A8.1_VH.06QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSSLRSDDTAVYYCAREGGTYNWFDPWG QGTLVTVSS (SEQID NO: 1990) >52A8.1_VKDIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID NO:1922) >52A8.1_VH.07QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPNSAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNYFDPWG QGTLVTVSS (SEQID NO: 1991) >54A1.1_N83D_VK.01DIQMTQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1992) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.02DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQQKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1993) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.03DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1994) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.04DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTLTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1995) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.05DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDFATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1996) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.06DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDVATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1997) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.07DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGGGTKVDIKR (SEQ ID NO:1998) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VK.08DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTKVDIKR (SEQ ID NO:1999) >54A1.1_N83D_VHQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 1925) >54A1.1_N83D_VKDIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1924) >54A1.1_N83D_VH.09QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 2000) >54A1.1_N83D_VKDIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1924) >54A1.1_N83D_VH.10QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGYMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW GQGTMVTVSS (SEQID NO: 2001) >54A1.1_N83D_VKDIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID NO:1924) >54A1.1_N83D_VH.11QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPHSGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNYNYGAFDFW GQGTMVTVSS (SEQID NO: 2002) >58C2.1_VK.01ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDEGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ ID NO:2003) >58C2.1_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYPYYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 1929) >58C2.1_VKENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ ID NO:1928) >58C2.1_VH.02QVQLVESGGGVVQPGGSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYPYYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2004) >58C2.1_VKENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ ID NO:1928) >58C2.1_VH.03QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNEGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYPYYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2005) >58C2.1_VKENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ ID NO:1928) >58C2.1_VH.04QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNDGNNKYYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYPYYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2006) >58C2.1_VKENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ ID NO:1928) >58C2.1_VH.05QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWQGYPYYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2007) >56E7.3_VK.01DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:2008) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK.02DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:2009) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK.03DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDFATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:2010) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK.04DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGGGTTVDIKR (SEQ ID NO:2011) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK.05DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGQGTTVDIKR (SEQ ID NO:2012) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK.06DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTKVDIKR (SEQ ID NO:2013) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK.07DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTRVDIKR (SEQ ID NO:2014) >56E7.3_VHEVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 1927) >56E7.3_VK378DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:1926) >56E7.3_VH.08EVQLVQSGPEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLVT VSS (SEQ IDNO: 2015) >56E7.3_VKDLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:1926) >56E7.3_VH.09EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGESDTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLVT VSS (SEQ IDNO: 2016) >56E7.3_VKDLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:1926) >56E7.3_VH.10EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 2017) >56E7.3_VKDLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID NO:1926) >56E7.3_VH.11EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADTSISTAYLQWSSLKASDTAVYYCARAQLGIFDYWGQGTLV TVSS (SEQ IDNO: 2018) >60D7.1_N30T_VK.01DIVLTQTPLSLPVTPGEPASISCRSSQSLLESDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:2019) >60D7.1_N30T_VHQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 1931) >60D7.1_N30T_VK.02DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDEGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:2020) >60D7.1_N30T_VHQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 1931) >60D7.1_N30T_VKDIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:2021) >60D7.1_N30T_VH.03QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 2022) >60D7.1_N30T_VKDIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:2021) >60D7.1_N30T_VH.04QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYEGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 2023) >60D7.1_N30T_VKDIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:2021) >60D7.1_N30T_VH.05QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 2024) >60D7.1_N30T_VKDIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ ID NO:2021) >60D7.1_N30T_VH.06QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFYSGYPFFYYYGMDVWGQGTTVTVSS (SEQ ID NO: 2025) >63A10.1_C58S_VL.01SYELTQPLSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2026) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.02SYELTQPPSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2027) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.03SYELTQPHSVSVALAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2028) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.04SYELTQPHSVSVAPAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2029) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.05SYELTQPHSVSVATGQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2030) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.06SYELTQPHSVSVATAQTARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2031) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.07SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQAPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2032) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.08SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQSPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2033) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.09SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQFPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2034) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.10SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSESNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2035) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.11SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNSGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2036) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.12SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIQAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:2037) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.13SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWESSSDGVFGGGTKLTVLG (SEQ ID NO:2038) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VL.14SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSEGVFGGGTKLTVLG (SEQ ID NO:2039) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.15EVQLVESGGGLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2040) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.16EVQLVESGGDLVQPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2041) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.17EVQLVESGGDLVKPGGSLRLSCAVSGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVED YFDYWGQGTLVTVSS(SEQ ID NO: 2042) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.18EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVSRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2043) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.19EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTEGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2044) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.20EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDDSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2045) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.21EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDNSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2046) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.22EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKAEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2047) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.23EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCATDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2048) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.24EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTRDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2049) >63A10.1_C58S_VLSYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID NO:1932) >63A10.1_C58S_VH.25EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTESSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 2050) >63A10.1_C58S_VL.26SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTATLTISRIEAGDEADYYCQVYDSSSDGVFGGGTKLTVLG (SEQ ID NO:2051) >63A10.1_C58S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1933) >63A10.3_N20R_C42S_VL.01SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKPGQSPVLVIYQDSERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTVLG (SEQ ID NO:2052) >63A10.3_N20R_C42S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1935) >63A10.3_N20R_C42S_VL.02SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKSGQSPVLVIYQESERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTVLG (SEQ ID NO:2053) >63A10.3_N20R_C42S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1935) >63A10.3_N20R_C42S_VL.03SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKSGQSPVLVIYQDSERPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWESTTVVFGGGTKLTVLG (SEQ ID NO:2054) >63A10.3_N20R_C42S_VHEVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF DYWGQGTLVTVSS(SEQ ID NO: 1935) >64B10.1_VL.01QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLAITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:2055) >64B10.1_VHQIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTTVTVSS (SEQID NO: 1937) >64B10.1_VL.02QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG 20IPDRFSGSKSGTSATLGITGLQTEDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:2056) >64B10.1_VHQIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTTVTVSS (SEQID NO: 1937) >64B10.1_VL.03QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWESSLSAVVFGGGTKLTVLG (SEQ ID NO:2057) >64B10.1_VHQIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTTVTVSS (SEQID NO: 1937) >64B10.1_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1936) >64B10.1_VH.04QIQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTTVTVSS (SEQID NO: 2058) >64B10.1_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1935) >64B10.1_VH.05QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTLVTVSS (SEQID NO: 2059) >64B10.1_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1935) >64B10.1_VH.06QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTMVTVSS (SEQID NO: 2060) >64B10.1_VL.07QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTYDSSLSAVVFGGGTKLTVLG (SEQ ID NO:2061) >64B10.1_VHQIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG QGTTVTVSS (SEQID NO: 1937) >64B10.1_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1935) >64B10.1_VH.08QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTYDYYYGVDVWG QGTTVTVSS (SEQID NO: 2062) >66G2_VK.01DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:2063) >66G2_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 1939) >66G2_VK.02DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTEFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:2064) >66G2_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 1939) >66G2_VK.03DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTDFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:2065) >66G2_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 1939) >66G2_VK.04DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLQGYPLTFGGGTKVEIKR (SEQ ID NO:2066) >66G2_VH QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 1939) >66G2_VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2_VH.05QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 2067) >66G2_VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2_VH.06QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYEGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGMD VWGQGTTVTVSS(SEQ ID NO: 2068) >66G2_VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2_VH.07QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYAESVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGMD VWGQGTTVTVSS(SEQ ID NO: 2068) >66G2_VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2_VH.08QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRFTISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 2070) >66G2_VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2_VH.09QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCAKTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 2071) >66G2_VKDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID NO:1938) >66G2_VH.10QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDGSNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCARTVTKEDYYYYGM DVWGQGTTVTVSS(SEQ ID NO: 2072) >67F5_VK.01ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIYGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:2073) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67F5_VK.02ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLESADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:2074) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67F5_VK.03ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQPADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:2075) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67F5_VK.04ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSEDFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:2076) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67F5_VK.05ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYYCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:2077) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67F5_VKENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID NO:1940) >67F5_VH.06QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 2078) >67F5_VK.07ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIYPWTFGQGTKVEIKR (SEQ ID NO:2079) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67F5_VK.08ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPYTFGQGTKVEIKR (SEQ ID NO:2080) >67F5_VHQVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL VTVSS (SEQ IDNO: 1941) >67C10_VK.01DIVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ ID NO:2081) >67C10_VH EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW GQGTMVTVSS(SEQ ID NO: 1943) >67C10_VK.02DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDEGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ ID NO:2082) >67C10_VH EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW GQGTMVTVSS(SEQ ID NO: 1943) >67C10_VKDFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ ID NO:1942) >67C10_VH.03EVQLVQSGAEVKKPGESLKISCKGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW GQGTMVTVSS(SEQ ID NO: 2083) >67C10_VKDFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ ID NO:1942) >67C10_VH.04EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGESDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIWG QGTMVTVSS (SEQID NO: 2084) >68C8_VL.01QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLAITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:2085) >68C8_VH QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 1945) >68C8_VL.02QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTEDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:2086) >68C8_VH QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 1945) >68C8_VL.03QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWESSLSAVVFGGGTKLTVLG (SEQ ID NO:2087) >68C8_VH QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 1945) >68C8_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8_VH.04QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 2088) >68C8_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8_VH.05QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLDTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 2089) >68C8_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8_VH.06QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCARYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 2090) >68C8_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8_VH.07QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTLVTVSS (SEQID NO: 2091) >68C8_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8_VH.08QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTMVTVSS (SEQID NO: 2092) >68C8_VL.09QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTYDSSLSAVVFGGGTKLTVLG (SEQ ID NO:2093) >68C8_VH QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW GQGTTVTVSS (SEQID NO: 1945) >68C8_VLQSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ ID NO:1944) >68C8_VH.10QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDYDYYYGMDVW GQGTTVTVSS (SEQID NO: 2094)

Example 14 Immunogenicity Prediction

Immune responses against proteins are enhanced by antigen processing andpresentation in the major histocompatability complex (MHC) class IIbinding site. This interaction is required for T cell help in maturationof antibodies that recognize the protein. Since the binding sites of MHCclass II molecules have been characterized, it is possible to predictwhether proteins have specific sequences that can bind to a series ofcommon human alleles. Computer algorithms have been created based onliterature references and MHC class II crystal structures to determinewhether linear 9 amino acid peptide sequences have the potential tobreak immune tolerance. We used the TEPITOPE™ program called todetermine if point mutations of FGF21 are predicted to increase antigenspecific T-cells in a majority of humans. Based on the linear proteinsequence, none of the mutations examined are expected enhanceimmunogenicity. Results are shown in Table 17A and Table 17B below.

TABLE 17A Protein Predicted Immunogenicity Met-FGF21 LowMet-hFGF21(N106D) Low Met-FGF21 (N122D) Low hFc(R4).L15.hFGF21(G170E)Low hFc(R4).L15.hFGF21(P171A) Low hFc(R4).L15.hFGF21(S172L) Lowp30.hFc.L15.hFGF21(A45K, G170E) Low p30.hFc.L15.hFGF21 (L98R, P171G) Low

TABLE 17B LC HC Non- Non- LC LC Non- Tolerant HC HC Non- tolerantPredicted LC Total Tolerant Tolerant HLA HC Total Tolerant tolerant HLAClone immunogenicity Agretopes Agretopes Agretopes DRB1 AgretopesAgretopes Agretopes DRB1 68C8 Tier 1 3 3 0 NA 12 12 0 NA 63A10 Tier 1 11 0 NA 12 12 0 NA 51A8 Tier 2 3 2 1 0101 16 16 0 NA 0701 51E5 Tier 2 6 60 NA 11 10 1 0401 0701 64B10 Tier 2 2 2 0 NA 12 11 1 0801 49H12 Tier 3 75 2 0101 13 13 0 NA 0701 0801 1301 1501 54A1 Tier 3 6 4 2 0301 14 14 0NA 0801 1501 52A8 Tier 3 6 5 1 0701 13 12 1 1301 60D7 Tier 4 8 7 1 030116 14 2 0401 0401 1501 1101 49C8 Tier 4 7 5 2 0801 14 13 1 0401 150167C10 Tier 4 8 7 1 0301 14 12 2 0101 0401  701 1101

Each reference cited herein is incorporated by reference in its entiretyfor all that it teaches and for all purposes.

The present disclosure is not to be limited in scope by the specificembodiments described herein, which are intended as illustrations ofindividual aspects of the disclosure, and functionally equivalentmethods and components form aspects of the disclosure. Indeed, variousmodifications of the disclosure, in addition to those shown anddescribed herein will become apparent to those skilled in the art fromthe foregoing description and accompanying drawings. Such modificationsare intended to fall within the scope of the appended claims.

1-23. (canceled)
 24. A method of preventing or treating a condition in asubject in need of such treatment comprising administering atherapeutically effective amount of isolated antigen binding proteinthat induces FGF21-mediated signaling, wherein the antigen bindingprotein comprises a light chain CDR1 comprising a sequence of SEQ ID NO:821, a light chain CDR2 comprising a sequence of SEQ ID NO: 900, a lightchain CDR3 comprising a sequence of SEQ ID NO: 954, a heavy chain CDR1comprising a sequence of SEQ ID NO: 611, a heavy chain CDR2 comprising asequence of SEQ ID NO: 664, and a heavy chain CDR3 comprising a sequenceof SEQ ID NO: 741 to the subject, wherein the condition is treatable bylowering one or more of blood glucose, insulin or serum lipid levels.25. The method of claim 24, wherein the antigen binding proteincomprises one or more of: (a) a light chain variable domain sequencecomprising V_(L)47 of Table 2A (SEQ ID NO. 263); (b) a heavy chainvariable domain sequence comprising V_(H)46 of Table 2B (SEQ ID NO:361); or (c) a combination comprising a light chain variable domain of(a) and a heavy chain variable domain of (b).
 26. The method of claim25, wherein the light chain variable domain and the heavy chain variabledomain comprise V_(L)47 and V_(H)46.
 27. The method of claim 26, whereinthe antigen binding protein comprises: (a) a kappa light chain constantsequence of SEQ ID NO: 12 (b) a lambda light chain constant sequence ofSEQ ID NO: 13 (c) a heavy chain constant sequence of SEQ ID NO: 11; or(d) (i) the kappa light chain constant sequence of SEQ ID NO: 12 or thelambda light chain constant sequence of SEQ ID NO: 13, and (ii) theheavy chain constant sequence of SEQ ID NO:
 11. 28. The method of claim24, wherein the antigen binding protein is a human antibody, a humanizedantibody, chimeric antibody, a monoclonal antibody, a polyclonalantibody, a recombinant antibody, an antigen-binding antibody fragment,a single chain antibody, a diabody, a triabody, a tetrabody, a Fabfragment, an F(fab′)₂ fragment, an IgD antibody, an IgE antibody, an IgMantibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, an IgG4antibody, or an IgG4 antibody having at least one mutation in the hingeregion.
 29. The method of claim 24, wherein the condition is diabetes,obesity, dyslipidemia, NASH, cardiovascular disease or metabolicsyndrome.
 30. The method of claim 29, wherein the condition is type 2diabetes.